Abstract
OBJECTIVES
This study aimed to investigate the characteristics of a reduced right ventricular distensibility after heart transplant.
METHODS
This study enrolled 64 adult patients who underwent heart transplant at our institution. The degree of right ventricular distensibility was quantified by calculating the difference between right atrial pressures (RAPs) of X descent and Y descent (X–Y) from the RAP waveform in right heart catheterization. Histologically, the ratio of the interstitial tissue in myocardial biopsy samples was calculated.
RESULTS
Of the 64 patients, 35 (55%) had a reduced right ventricular distensibility at 1 week after heart transplant (X–Y > 1 mmHg, RD group), and 29 (45%) had a normal right ventricular distensibility (X–Y ≤ 1 mmHg, ND group). The mean RAP and mean pulmonary capillary wedge pressure 1 week after heart transplant in the RD group were significantly higher than that in the ND group. The mean RAP and mean pulmonary capillary wedge pressure in the RD group gradually normalized 12 weeks postoperation. The ratio of the interstitial tissue of biopsy samples significantly correlated with the X–Y value. The number of patients who required inotropic support >14 days was higher in the RD group than in the ND group.
CONCLUSIONS
Reduced donor heart distensibility was a common impairment early after heart transplant. It might result from interstitial oedema in the myocardial tissue of the donor heart. Reduced donor heart distensibility after heart transplant might be associated with early clinical outcomes; however, further investigation is required.
Keywords: Donor heart, Heart transplant, Haemodynamics, Ventricular distensibility
INTRODUCTION
Cardiac graft function after orthotropic heart transplant (OHT) is the main determinant of post-OHT clinical results. Donor heart function and its haemodynamics are usually evaluated by intracardiac right- and left-sided pressures, such as right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP), as well as echocardiography. Previous studies reported that acute allograft rejection can cause restrictive haemodynamics [1, 2], whereas previous studies reported that restrictive haemodynamic pattern at the early period post-OHT is common even in patients without acute rejection [3, 4]. However, the detailed aetiology and clinical course of the haemodynamic pattern and its effect on clinical outcomes after OHT remain unclear.
Ventricular distensibility is related to the diastolic function of the ventricle, and ventricular distensibility disorder can be defined by the upward shift in the ventricular diastolic pressure–volume relationship, which is also seen in several diseases of the myocardium and pericardium [5, 6]. These conditions result in high atrial pressure and abrupt cessation of ventricular filling. Previous studies revealed that a reduced-distensible type of RAP waveform is seen in patients with right ventricle infarction and is representative of the restricted expansion of the damaged myocardium [7, 8]. Some aetiologies of ventricular distensibility disorder have been reported up to date [5, 6, 9–12]; however, little has been known in OHT patients. Therefore, this study aimed to investigate the characteristics of a reduced right ventricular distensibility using RAP waveform and myocardial biopsy sample after OHT.
MATERIALS AND METHODS
Patients and study design
This retrospective observational study using data already collected was approved by the Ethics Committee of Osaka University Hospital (17026, 25 May 2017) and was conducted in accordance with the Declaration of Helsinki. We obtained written informed consent for the use of case data from the patients or from the family members of deceased patients.
A consecutive series of 78 adult patients who underwent OHT at our institution between 2007 and 2018 were enrolled in the study. We excluded four patients whose haemodynamics could not be evaluated because they required mechanical circulatory support, such as intraoperative aortic balloon pumping and extracorporeal membrane oxygenation after OHT. We excluded two patients who had an episode of acute cellular rejection and one patient with antibody-mediated rejection 1 week post-OHT. Seven patients were excluded because optimal RAP waveform was not detected. Finally, 64 patients were analysed (Fig. 1A).
Figure 1:
Flow chart showing patient enrolment and analysis of the right atrial waveform of endomyocardial biopsy samples. (A) Flow chart showing patient enrolment in this study. (B) RAP waveform obtained from patients with normal right ventricular distensibility and (C) with reduced right ventricular distensibility. (D) Endomyocardial biopsy samples stained with Masson trichrome and (E) analysed using the Dynamic Cell Count function of the BZ-II Analyzer Software. The pink and green areas indicate the interstitial and myocardial tissues, respectively. ECG: electrocardiography; RAP: right atrial pressure; RHC: right heart catheterization.
Surgical procedure of heart transplant and immunosuppressive therapy
Patients underwent OHT using a modified bicaval technique as previously described [11]. Intravenous methylprednisolone sodium (500 mg) was administered immediately before reperfusion of the donor heart. Immunosuppression therapy was initiated with prednisolone, mycophenolate mofetil and tacrolimus. Everolimus is usually initiated at 3–12 months if patients exhibit any of the following: coronary artery plaque, mycophenolate mofetil-related leucocytopaenia, tacrolimus-related renal impairment or episode of cytomegalovirus infection.
Right heart catheterization and histological assessment
At our institute, right heart catheterization (RHC) is routinely performed to evaluate donor heart function according to the following schedule: 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24 weeks, 1 year after OHT, and annually thereafter.
In this study, RAP waveforms, which were obtained at 1 week post-OHT, were analysed. According to the established significance of jugular venous waveform [13–15], two cardiologists, who were blinded to clinical data, evaluated the RAP waveform. We judged that the RAP waveform was optimally obtained during RHC when the a wave, c wave, v wave, X decent and Y decent were recognized by both cardiologists. In a patient with normal right ventricular distensibility, the X descent nadir is usually deeper than that of Y descent. When the nadir of Y descent was deeper than that of X descent, the RA pressure waveform had a dominant Y descent, which is highly indicative of reduced right ventricular distensibility [7–9]. In this study, we defined the RAP waveform, which had a dominant Y descent where the nadir of Y descent was 1 mmHg deeper than that of X descent, as a finding highly indicative of reduced right ventricular distensibility. For example, Fig. 1B shows a normal RAP waveform characterized by the highest a wave and the lowest X descent within one cardiac cycle. By contrast, Fig. 1C shows the dominant Y descent with 1 mmHg lower nadir than that of X descent, which was regarded as a finding highly indicative of a reduced right ventricular distensibility [13–15]. In addition, the degree of right heart distensibility was quantified by calculating the difference between the RAP of X descent and that of Y descent (X–Y) from the RAP waveform. Therefore, a larger value of X–Y indicates more severely impaired distensibility of the right ventricle. Patients were divided into two groups: patients with normal right ventricular distensibility (X–Y ≤ 1 mmHg) 1 week after OHT [normal distensibility of right ventricle (ND) group; Fig. 1B] or with reduced right ventricular distensibility (X–Y > 1 mmHg) [reduced distensibility of right ventricle (RD) group; Fig. 1C]. Additionally, massive pericardial effusion or cardiac tamponade was excluded by echocardiography within 1 week after heart transplant.
In our institution, for the evaluation of rejection, routine endomyocardial biopsy samples (usually 3 or 4 samples from each procedure) were obtained from the right ventricle of the donor heart using a conventional technique simultaneously. The biopsy samples were fixed in buffered formalin, embedded in paraffin, serially sectioned at 3–4 μm and stained with Masson trichrome. For histological assessment of the donor heart, the ratio of the interstitial tissue in biopsy samples, which were obtained 1 week after OHT, was automatically analysed using the Dynamic Cell Count function of the BZ-II Analyzer Software (KEYENCE) with a BZ-X700 microscope (KEYENCE) (Fig. 1D and E). First, we made the BZ-II Analyzer Software recognize the brown and blue areas in the biopsy samples subjected to Masson trichrome staining as the whole area of the myocardial tissue. Then, the brown area in the biopsy samples was also recognized as cardiomyocyte. After the recognition, interstitial and myocardial tissues were automatically classified into pink and green areas, respectively (Fig. 1E). The ratio of the interstitial tissue was calculated by dividing the area of the interstitial tissue (pink area) by the whole area of the myocardial tissue in the samples (pink area + green area) (Fig. 1E).
Statistical analysis
Preoperative, intraoperative and postoperative variables were compared between the two groups using Wilcoxon’s rank sum test for continuous variables and Fisher’s exact test for categorical variables. We assessed the correlation between the perioperative factors using the Pearson product–moment correlation coefficient. A P-value <0.05 was considered significant. The trends of the time course of the RHC parameters were analysed using multilevel regression analysis for repeatable measured variables. The differences over time and in the repeated measures across subjects for both the whole model and each effect were evaluated. The RHC parameters at each time point were compared with those 1 week after OHT using the paired t-test. In this analysis, we used the Bonferroni–Holm correction methods. A P-value <0.007 (0.05/7) was considered significant because seven time points were evaluated. Values are presented as means with standard deviations and medians with interquartile ranges. Statistical analyses were performed using JMP Pro version 11.2.0 (SAS Institute, Cary, NC, USA).
RESULTS
Perioperative characteristics
Changes in each haemodynamic parameter after OHT in all patients are shown in Fig. 2. The RHC parameters were significantly different over time. The mean PCWP (mPCWP) and mean RAP (mRAP) were highest at 1 week after OHT and significantly decreased from week 4 after OHT (Fig. 2A and B), whereas the mean cardiac index significantly increased from week 8 after OHT (Fig. 2C).
Figure 2:
Time course of the parameters in right heart catheterization early after heart transplant. (A) Mean PCWP, (B) mean RAP and (C) mean CI in all patients. The P-value indicates the level of statistical significance of the differences over time model. CI: cardiac index; PCWP: pulmonary capillary wedge pressure; RAP: right atrial pressure. *P for <0.001 (vs 1 week after orthotropic heart transplant, respectively).
In our cohort, 35 patients (55%) were recognized to have reduced right ventricular distensibility at 1 week after OHT (RD group), and the remaining 29 patients (45%) had a normal right ventricular distensibility (ND group). On the comparison of preoperative and intraoperative factors, no significant differences in donor age, cause of death, cardiac function and wall thickness were found between the two groups. Moreover, no difference in the ischaemic time of the donor heart was noted between the groups. Cardiopulmonary bypass (CPB) time was longer in patients in the RD group (Table 1). In the 35 RD group patients, reduced distensibility remained in 13 (37%) patients, whereas 22 (63%) recovered the normal distensibility of the right ventricle until 8 weeks after OHT.
Table 1:
Baseline characteristics and operative parameters of recipients and donors
| Total (n = 64) | ND (n = 29) | RD (n = 35) | P-value | |
|---|---|---|---|---|
| Recipient factor | ||||
| Age (years) | 40 ± 14 | 44 ± 13 | 37 ± 14 | 0.061 |
| Sex (male) | 44 (69) | 22 (76) | 22 (63) | 0.26 |
| BMI (kg/m2) | 20.4 ± 3.4 | 20.2 ± 3.3 | 20.6 ± 2.9 | 0.67 |
| Diagnosis | ||||
| ICM | 8 (13) | 5 (17) | 3 (9) | 0.30 |
| DCM | 39 (61) | 17 (59) | 22 (63) | |
| Others | 17 (27) | 7 (24) | 10 (29) | |
| Preoperative haemodynamics | ||||
| Preoperative inotropes | 6 (9) | 2 (7) | 4 (12) | 0.48 |
| LVAD implantation | 62 (97) | 27 (93) | 33 (94) | 0.85 |
| Mean duration of LVAD support (days) | 979 ± 316 | 1055 ± 302 | 917 ± 319 | 0.093 |
| Laboratory data | ||||
| Alb (g/dl) | 4.2 ± 0.6 | 4.2 ± 0.7 | 4.2 ± 0.5 | 0.80 |
| T-bil (mg/dl) | 0.86 ± 0.61 | 0.91 ± 0.77 | 0.83 ± 0.44 | 0.82 |
| Cr (mg/dl) | 0.92 ± 0.31 | 0.87 ± 0.23 | 0.97 ± 0.36 | 0.60 |
| CRP (mg/dl) | 0.14 (0.05–0.67) | 0.11 (0.04–0.42) | 0.24 (0.06–0.70) | 0.23 |
| BNP (pg/ml) | 131.1 (62.1–239.3) | 178.3 (73.6–292.4) | 123.9 (55.7–221.2) | 0.40 |
| WBC (×103/ml) | 6.4 ± 1.5 | 6.6 ± 1.4 | 6.2 ± 1.5 | 0.16 |
| Hb (g/dl) | 12.1 ± 1.7 | 12.2 ± 1.4 | 12.1 ± 1.9 | 0.79 |
| Plt (×104/μl) | 19.4 ± 6.2 | 20.4 ± 5.6 | 18.6 ± 6.6 | 0.13 |
| Donor factor | ||||
| Age | 42 ± 12 | 39 ± 12 | 44 ± 12 | 0.16 |
| Sex (male) | 44 (69) | 23 (79) | 21 (60) | 0.093 |
| Cardiac arrest | 32 (50) | 13 (44) | 19 (54) | 0.45 |
| Cause of brain death | ||||
| Brain haemorrhage | 44 (69) | 22 (76) | 22 (63) | 0.48 |
| Suffocation | 10 (16) | 3 (14) | 7 (20) | |
| Drowning | 3 (5) | 1 (3) | 2 (6) | |
| Trauma | 2 (3) | 0 (0) | 2 (6) | |
| Others | 5 (8) | 3 (14) | 2 (6) | |
| Inotrope usage | 28 (44) | 12 (41) | 16 (46) | 0.73 |
| Echocardiogram | ||||
| LV ejection fraction (%) | 66.7 ± 8.3 | 65.3 ± 8.0 | 68.0 ± 8.5 | 0.21 |
| LVDd (mm) | 45.6 ± 5.1 | 46.2 ± 5.6 | 45.1 ± 4.8 | 0.43 |
| LVDs (mm) | 28.5 ± 5.0 | 29.4 ± 3.9 | 27.7 ± 5.7 | 0.16 |
| PWD (mm) | 10.8 ± 3.0 | 11.0 ± 2.9 | 10.7 ± 3.2 | 0.67 |
| IVSD (mm) | 10.1 ± 2.6 | 10.1 ± 2.3 | 10.1 ± 1.8 | 0.90 |
| Intraoperative factors | ||||
| CPB time (min) | 191 ± 45 | 179 ± 30 | 201 ± 52 | 0.039 |
| Ischaemic time (min) | 205 ± 43 | 205 ± 40 | 205 ± 46 | 0.96 |
| Haemorrhage (ml) | 4704 ± 2755 | 4613 ± 2606 | 4777 ± 2903 | 0.82 |
| Transfusion (ml) | 6076 ± 2998 | 5752 ± 3057 | 6336 ± 2970 | 0.45 |
| Donor/recipient weight ratio | 1.23 ± 0.33 | 1.31 ± 0.38 | 1.17 ± 0.28 | 0.11 |
| Donor–recipient sex mismatch | 15 (23) | 4 (14) | 11 (31) | 0.091 |
| Male to female | 7 (11) | 2 (7) | 5 (14) | 0.34 |
| Female to male | 8 (13) | 2 (7) | 6 (17) | 0.21 |
| Weight mismatch >±20% | 33 (52) | 19 (66) | 14 (40) | 0.50 |
Data are presented as the mean ± standard deviation or median with the 25th and 75th percentiles for continuous variables and counts (percentages) for categorical variables.
Alb: albumin; BMI: body mass index; BNP: brain natriuretic peptide; CPB: cardiopulmonary bypass; CRP: C-reactive protein; DCM: dilated cardiomyopathy; Hb: hemoglobin; ICM: ischaemic cardiomyopathy; IVSD: interventricular septum diameter; LV: left ventricle; LVAD: left ventricular assist device; LVDd: left ventricular diameter at end-diastole; LVDs: left ventricular diameter at end-systole; ND: normal distensibility; Plt: platelet; PWD: posterior left ventricular wall diameter; RD: reduced distensibility; WBC: white blood cell.
Relationship between right heart catheterization parameters, histological analysis and perioperative factors
One week after OHT, the mean pulmonary artery pressure, mRAP and mPCWP in the RD group were significantly higher than those in the ND group, but no differences in cardiac output and pulmonary vascular resistance were found (Table 2). The ratio of the interstitial tissue in biopsy samples in the RD group was significantly higher than that in the ND group (50 ± 8% vs 44 ± 8%, P = 0.005) (Table 2).
Table 2:
Parameters in right heart catheterization and histological analysis of endomyocardial biopsy sample at 1 week after heart transplant
| Total (n = 64) | ND (n = 29) | RD (n = 35) | P-value | |
|---|---|---|---|---|
| Systolic PAP (mmHg) | 27.5 ± 7.1 | 23.6 ± 4.3 | 30.7 ± 7.5 | <0.001 |
| Diastolic PAP (mmHg) | 12.8 ± 4.7 | 10.3 ± 3.4 | 14.8 ± 4.7 | <0.001 |
| Mean PAP (mmHg) | 19.0 ± 5.5 | 15.9 ± 3.4 | 21.6 ± 5.6 | <0.001 |
| Mean RAP (mmHg) | 7.9 ± 4.3 | 5.1 ± 1.6 | 10.2 ± 4.3 | <0.001 |
| Mean PCWP (mmHg) | 12.4 ± 4.7 | 9.4 ± 3.0 | 14.9 ± 4.4 | <0.001 |
| Heart rate (bpm) | 94 ± 19 | 95 ± 16 | 94 ± 22 | 0.39 |
| CO (l/min) | 4.7 ± 1.2 | 4.6 ± 1.2 | 4.9 ± 1.1 | 0.26 |
| CI (l/min/m2) | 2.9 ± 0.7 | 2.8 ± 0.7 | 3.0 ± 0.7 | 0.18 |
| SV (ml) | 52 ± 15 | 50 ± 16 | 54 ± 14 | 0.24 |
| PVR (wood unit) | 1.45 ± 0.73 | 1.53 ± 0.69 | 1.37 ± 0.77 | 0.38 |
| RAP/SV ratio (mmHg/ml) | 0.15 (0.09–0.19) | 0.10 (0.07–0.14) | 0.18 (0.14–0.21) | <0.001 |
| Transpulmonary gradient (mmHg) | 7.0 (5.0–7.0) | 6.5 (5.3–7.8) | 7.0 (4–7.0) | 0.78 |
| Ratio of interstitial tissue (%) | 48.6 ± 8.1 | 44.0 ± 8.0 | 49.6 ± 7.5 | 0.005 |
Data are presented as the mean ± standard deviation or median with the 25th and 75th percentiles for continuous variables.
bpm: beat per minute; CI: cardiac index; CO: cardiac output; ND: normal distensibility; PAP: pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; PVR: pulmonary vascular resistance; RAP: right atrial pressure; RD: reduced distensibility; SV: stroke volume.
On the evaluation of the relationship between the X–Y value and each parameter, the X–Y value at 1 week had strong positive correlation with the mPCWP, as well as with mRAP (vs mPCWP; R = 0.62 vs mRAP; R = 0.74, P < 0.001, respectively) (Fig. 3A and B). The correlations of the mPCWP, mRAP and the ratio of the interstitial tissue are also shown in Fig. 3C and D (vs mPCWP: R = 0.40, P = 0.002 vs mRAP: R = 0.41, P = 0.001). Moreover, the ratio of the interstitial tissue of biopsy samples had significant correlation with the X–Y value (R = 0.43, P < 0.001) (Fig. 3E). The X–Y value had a significant positive correlation with the CPB time (R = 0.26, P = 0.040) (Fig. 3F). Moreover, significant correlation was found between the CPB time and interstitial tissue ratio (R = 0.33, P = 0.010) (Fig. 3G).
Figure 3:
Relationship among perioperative parameters, parameters obtained by right heart catheterization and histological analysis. (A) Correlation of mean PCWP and the difference between RAP of X descent and that of Y descent. (B) Correlation of mean RAP and the difference between RAP of X descent and that of Y descent. (C) Correlation of mean PCWP and the ratio of interstitial tissue in endomyocardial biopsy samples. (D) Correlation of mean RAP and the ratio of interstitial tissue in endomyocardial biopsy samples. (E) Correlation of the difference between RAP of X descent and that of Y descent and the ratio of interstitial tissue in endomyocardial biopsy samples. (F) Correlation of CPB time and the difference between RAP of X descent and that of Y descent. (G) Correlation of CPB time and the ratio of interstitial tissue in endomyocardial biopsy samples. Red area in the figure indicates 95% confidence interval. CPB: cardiopulmonary bypass; PCWP: pulmonary capillary wedge pressure; RAP: right atrial pressure.
Change in haemodynamic parameters in the normal distensibility and reduced distensibility groups after orthotropic heart transplant
Changes in each parameter in both the ND and RD groups are shown in Fig. 4. The mPCWP and mRAP were significantly different in the repeated measures across subjects for the overtime model. The mPCWP and mRAP in the RD group were highest early after OHT and significantly higher than those in the ND group until week 4 and 8, respectively; however, these parameters gradually normalized until week 12 postoperatively and were maintained thereafter (Fig. 4A and B). Meanwhile, the mean cardiac index between the two groups were both preserved throughout the postoperative period (Fig. 4C).
Figure 4:
Time course of the parameters in right heart catheterization after heart transplant. (A) Mean PCWP, (B) mean RAP and (C) mean CI in patients with normal and reduced right ventricular distensibility. The P-value indicates the level of statistical significance of the difference in the repeated measures across subjects for the whole model. CI: cardiac index; ND: normal distensibility; PCWP: pulmonary capillary wedge pressure; RAP: right atrial pressure; RD: reduced distensibility. *P < 0.005, **P < 0.001 (vs 1 week after orthotropic heart transplant, respectively).
Clinical outcomes
Postoperative outcomes are summarized in Table 3 and Fig. 5. Regarding early post-OHT results, there was a trend of a higher incidence of prolonged intensive care unit stay >14 days in the RD group than in the ND group [7 (20%) vs 1 (3%), P = 0.06]. The prevalence of patients who required prolonged inotropic support >14 days was higher in the RD group than in the ND group [8 (23%) vs 1 (3%), P = 0.03] (Table 3). However, the midterm overall survival showed no significant difference between the two groups (Fig. 5).
Table 3:
Early outcomes after heart transplant
| ND (n = 29) | RD (n = 35) | P-value | |
|---|---|---|---|
| Hospital death | 0 (0) | 1 (3) | NA |
| Death within 8 weeks after OHT | 0 (0) | 0 (0) | NA |
| Usage of mechanical support, n | 5 (17) | 7 (20) | 0.78 |
| Intubation time (h) | 37 (23–64) | 36 (23–61) | 0.27 |
| ICU stay ≥14 days, n | 1 (3) | 7 (20) | 0.063 |
| Catecholamine-dependent period ≥14 days, n | 1 (3) | 8 (23) | 0.038 |
Data are presented as median with the 25th and 75th percentiles for continuous variables and counts (percentages) for binary categorical variables.
ICU: intensive care unit; NA: not available; ND: normal distensibility; OHT: orthotropic heart transplant; RD: reduced distensibility.
Figure 5:
Kaplan–Meier curve showing freedom from all-cause mortality. ND: normal distensibility; RD: reduced distensibility.
DISCUSSION
This study revealed that more than half of the patients had reduced donor heart distensibility early after OHT. Patients with reduced right ventricular distensibility had significantly higher intracardiac pressure, such as mRAP and mPCWP, which gradually recovered over several months. Although patients with reduced right ventricular distensibility required longer CPB time during OHT surgery and longer postoperative inotropic support, the midterm result in patients with reduced right ventricular distensibility might be comparable with that in patients with normal distensibility.
The results of this study revealed that impaired right ventricular distensibility of the donor heart was common in the acute phase after heart transplant. In more than half of the patients who underwent OHT, the right atrial waveform obtained in the acute phase of OHT showed reduced distensibility, which was proven by the X–Y value of more than 1 mmHg. This waveform was perhaps caused by the compensatory change due to the reduced distensibility of the right ventricle, which could not fully receive venous return. This haemodynamic characteristic is similar to that in patients with constrictive pericarditis, restrictive cardiomyopathy or heart failure with preserved ejection fraction [14, 15]. We could not demonstrate echocardiographic data regarding diastolic function early after OHT. Studies reported that cardiac allograft may demonstrate abnormalities in the echocardiographic parameters of diastolic function which do not appear to correspond to true diastolic dysfunction [16, 17]. Okada et al. [18] also reported poor correlation between the clinical echocardiographic indices of diastolic function and PCWP. In this study, the X–Y value significantly correlated with mPCWP, which was reported as a parameter of diastolic dysfunction [19]. However, using PCWP may underestimate the reduced distensibility of the right ventricle, when high pulmonary vascular resistance exists. Moreover, RAP may be influenced by circulating blood volume. Samura et al. [20] reported that the RAP waveform in patients with left ventricular assist device was almost unchanged, although RAP was increased or reduced. This study suggests that analysing not only the haemodynamic parameters but also the waveform patterns is important to assess the reduced distensibility of the right ventricle. RAP waveform may be accurate in evaluating distensibility of right ventricle even under extracorporeal membrane oxygenation or intra-aortic balloon pumping. We also suspect that evaluating the RAP waveform at an earlier postoperative phase may be important for haemodynamic management. At bedside, we can monitor RAP waveform using Swan-Ganz catheter and judge whether the distensibility of the donor heart right ventricle is impaired early after OHT. Therefore, this monitoring might be useful for haemodynamic management including the inotropic regimen.
Our histological analysis of donor hearts 1 week post-OHT revealed that the ratio of the interstitial tissue in the myocardial tissue significantly correlated with mRAP, mPCWP and X–Y value, suggesting that increased interstitial tissue in the myocardial tissue may result in reduced donor heart distensibility. However, we could not clearly elucidate the risk factor for reduced right ventricular distensibility after OHT because preoperative donor data were similar between donor hearts with distensible and reduced-distensible functions after OHT. To the best of our knowledge, no study has evaluated the predictors of impaired right ventricular distensibility of donor hearts.
In this study, reduced distensibility, which was characterized by higher mRAP and mPCWP, gradually recovered over several months. This temporary impaired distensibility after OHT could be caused by myocardial oedema as well as interstitial fibrosis. Myocardial oedema will resolve until the chronic phase, while fibrosis will remain. Myocardial and intramyocardial oedema, which is one of the temporary changes of interstitial tissue [21–23], can increase ventricular diastolic stiffness after cardiac surgery [24–26]. Egan previously reported that myocardial ischaemia rather than CPB is related to myocardial oedema and postoperative dysfunction in animal models [27]. We suspect that a longer cardiac ischaemic time in OHT than that in other cardiac surgeries may cause severe myocardial oedema, which in turn may cause temporary ventricular diastolic dysfunction. However, several patients continued to have reduced right ventricular distensibility beyond 8 weeks after OHT, suggesting that myocardial fibrosis might also contribute to the increased interstitial ratio of the myocardial tissue. Disproportional accumulation of fibrous tissue is a major determinant of impaired stiffness, resulting in diastolic dysfunction [28]. A previous study showed that myocardial fibrosis develops early after OHT and increases gradually up to 2 months [29]. Indeed, mRAP in the RD group tended to be high compared with that in the ND group until midterm after OHT. This tendency between the groups might have occurred due to the differences in the severity of fibrosis in donor hearts. Long-term haemodynamic measurement of the donor heart and simultaneous histological analysis of biopsy samples would be required to evaluate the effect of donor heart fibrosis on its distensibility.
For postoperative outcomes, our data showed that patients with reduced right ventricular distensibility required longer CPB time and longer catecholamine-dependent postoperative period than those with normal right ventricular distensibility. We suspected that patients with reduced right ventricular distensibility might require longer CPB time than those with normal right ventricular distensibility because of the difficulty in withdrawing CPB due to the impaired distensibility of the right ventricle. On the contrary, the haemodynamics of the donor heart at midterm after OHT might not significantly differ between the groups. Considering these results, we believe that comparable survival and donor heart function at midterm after OHT might be achieved even in patients with reduced donor heart distensibility early after OHT, if the haemodynamics of these patients are maintained by inotropes until the donor heart recovers from impaired distensibility after OHT. However, further investigation is required to elucidate the effect of reduced donor heart distensibility early after OHT on midterm results.
Limitations
This study has some limitations. First, our study had a single-centre, retrospective design. Second, although RAP waveform is the main parameter in this study, we could not obtain optimal RAP waveform in seven patients who were excluded from our study. There were mainly two reasons why optimal RAP waveform was not obtained: (i) the disappearance of the X decent due to the attachment of the catheter tip to the tricuspid valve leaflet and (ii) the unclear Y decent due to the very short diastolic phase, because of tachycardia. However, we believed that this exclusion might not affect our main results. Third, histological analysis of the left ventricle was not performed. However, both RAP and PCWP were strongly correlated with the X–Y value, suggesting that impaired distensibility might occur not only in the right ventricle but also in the left ventricle. Fourth, our study could not evaluate the quantification of myocardial oedema in the donor heart. Considering the temporary physiological features early after OHT, we believed that the interstitial oedema might be a major consistent structural change in the myocardial tissue. Finally, we could only perform histological analysis using biopsy samples 1 week after OHT. Therefore, further studies using biopsy samples obtained in mid-term and long-term would be required.
CONCLUSION
This study confirmed that reduced donor heart distensibility is a common impairment early after OHT. It might result from interstitial oedema in the myocardial tissue of the donor heart. A relatively lower right distensibility of the donor heart after OHT might be associated with early clinical outcomes; however, further investigation would be required.
ACKNOWLEDGEMENT
This study was supported by the Clinical Investigator’s Research Project in Osaka University Graduate School of Medicine.
Conflict of interest: none declared.
Author contributions
Yuki Nakamura: Conceptualization; Methodology; Writing—original draft. Daisuke Yoshioka: Conceptualization; Methodology. Hidetsugu Asanoi: Conceptualization; Data curation; Formal analysis. Shigeru Miyagawa: Resources. Yasushi Yoshikawa: Resources. Hiroki Hata: Resources. Ryoto Sakaniwa: Formal analysis. Koichi Toda: Resources. Yoshiki Sawa: Conceptualization; Supervision.
Reviewer information
Interactive CardioVascular and Thoracic Surgery thanks Maurice Hogan, Markus Kamler, Mateo Marin-Cuartas and the other, anonymous reviewer(s) for their contribution to the peer-review process of this article.
ABBREVIATIONS
- CPB
Cardiopulmonary bypass
- mPCWP
Mean PCWP
- mRAP
Mean RAP
- ND
Normal distensibility
- OHT
Orthotropic heart transplant
- PCWP
Pulmonary capillary wedge pressure
- RAP
Right atrial pressure
- RD
Reduced distensibility
- RHC
Right heart catheterization
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