The clinical significance of intrapulmonary vascular dilations in liver transplant candidates

Intrapulmonary vascular dilations (IPVD) are common in patients with cirrhosis, but the majority do not have hepatopulmonary syndrome (HPS). The clinical significance of IPVD is unknown. Our aim was to determine the clinical impact due to the entire spectrum of IPVD in liver transplant (LT) candidates. A total of 122 evaluees for LT underwent contrast transthoracic echocardiography (cTTE). The degree of shunting was graded 1–3 (severe). HPS was defined as PaO₂ < 70 mmHg in the presence of IPVD and exclusion of other causes of hypoxemia. IPVD were detected in 57/122 (47%), and of these HPS was found in 5. IPVD were associated with higher Alveolar‐arterial (A‐a) gradients, with the highest occurring in patients with HPS (IPVD vs. no IPVD: p = 0.003; HPS vs. no IPVD: p = 0.004). All patients with HPS had grade 3 shunting, and had significantly widened A‐a gradient and lower PaO₂ compared with grade 1 or 2 IPVDs. Presence of IPVD did not affect survival measured from evaluation or after LT. Other clinical outcomes were also similar among patients with and without IPVD. IPVD are common among LT candidates. HPS is unlikely in presence of only mild to moderate shunting. Clinical outcomes are similar among patients with and without IPVD.     

Impact of mechanical circulatory support on pediatric heart transplant candidates with elevated pulmonary vascular resistance

With the new era of increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study was to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. The United Network for Organ Sharing (UNOS) database was used to identify patients aged 0‐18 at the time of listing for heart transplant between 2010 and 2019 who had PVR documented (n = 2081). Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No MCS groups, then divided by PVR (PVR) at the time of listing: <3, 3‐6, and >6 Wood units (WU). MCS was used in 20% overall (n = 426); 57% of those with PVR <3, 27% with PVR 3‐6, and 16% with PVR >6. MCS, PVR <3 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .049; vs. PVR 3‐6, P = .004; vs. PVR >6, P < .001). MCS, PVR 3‐6 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .048; vs. PVR 3‐6, P = .009; vs. PVR >6, P < .001). MCS, PVR >6 patients had a higher chance of positive waitlist outcome than No MCS, PVR >6 patients (P = .012). Within the No MCS group, patients with a PVR >6 had a higher incidence of negative waitlist outcome compared to PVR <3 (17% vs. 10%, P = .002); this was not the case in the MCS group (5% vs. 6%, P = .693). More patients in the MCS group were ventilator dependent (15% vs. 9%, P < .001) at the time of listing and less likely to have a functional status >50% (43% vs. 73%, P < .001). No significant differences in post‐transplant survival were found in pairwise comparisons of MCS and No MCS PVR subgroups. Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. This was most pronounced with a PVR greater than 6 WU. MCS compared to No MCS patients had better waitlist survival and equivalent post‐transplant survival. MCS patients, despite being more ill, had better overall survival regardless of PVR.     

血管活性物质在门肺高压症发病机制中的作用

目的 研究内皮素-1(ET-1)、一氧化氮(NO)、血栓素A2(TXA2)、前列环素(PGI2)、5 羟色胺(5-HT)和转移生长因子-β1(TGF-β1)在门肺高压症(PPHTN)发病机制中的作用.方法 对4 例PPHTN(P 组)和12 例PHT患者(C 组)进行病例-对照研究,另设10 例胃肠道肿瘤患者作为正常对...     

Role of echocardiography in detecting portopulmonary hypertension in liver transplant candidates

Portopulmonary hypertension (PPHTN) is a recognized complication of end-stage liver disease that adversely affects the outcome of orthotopic liver transplantation (OLT). There are limited data on the role of Doppler echocardiography in assessing pulmonary artery systolic pressure (PASP) in this population. The purpose of our study was to examine the accuracy of Doppler echocardiography in evaluating pulmonary artery pressures in liver transplant candidates. Clinical and demographic data were gathered retrospectively for 78 liver transplant candidates (48 men and 30 women, mean age 51 ± 9.6 yr) who had PASP determined both by right heart catheterization (RHC) and echocardiography. Paired sample t-test was used to compare mean PASP by echocardiography and RHC. Correlation of PASP between echocardiography and RHC was determined using Pearson's linear correlation. Positive and negative predictive values for echocardiography for PASP > 50 mmHg are reported as compared with RHC. The mean PASP by echocardiography (43.2 ± 12.3 mm Hg) was significantly higher than mean PASP by RHC (33.7 ± 15.5 mm Hg; P < .001). Regarding PASP, there was a significant but weak correlation between echocardiography and RHC (r = 0.46, P = .01). The positive and negative predictive values of echocardiography for identifying clinically significant pulmonary hypertension (PASP > 50 mm Hg) were 37.5% and 91.9%, respectively. Echocardiography is a useful tool in estimating PASP in liver transplant candidates. Patients with apparently elevated PASP by echocardiography should undergo invasive assessment by RHC before being excluded from liver transplant. (Liver Transpl 2002;8:1051-1054.)     

多普勒超声心动图筛查门肺高压症的临床研究

目的:调查门肺高压症在国内的发病情况,评估二维多普勒超声心动图作为筛查方法的临床效果。方法:于77例接受手术治疗的肝硬化门静脉高压症病人,行术前二维多普勒超声心动图检查,测算肺动脉收缩压和肺加速时间以筛查门肺高压症病人;并和标准诊断法右心导管法结果进行比较。结果:本研究样本人群中的门肺高压症发病率为3.9%,二维多普勒超声心动图筛查试验的灵敏度为100%,特异度为87.8%,真实度88.3%,阳性预测值为25%,阴性预测值为100%。结论:国内的门肺高压症发病情况与国际上报道的相似。二维多普勒超声心动图筛查法的灵敏度和阴性预测值高;阴性结果有助于排除门肺高压症,而阳性结果必须经右心导管法确诊。     

Severe pulmonary hypertension in liver transplant candidates

Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n = 102; mean pulmonary artery pressure, > 25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n = 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n = 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n = 7; systolic pulmonary artery pressure, > 60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate. (Liver Transpl Surg 1997 Sep;3(5):494-500)     

低氧性肺动脉高压的肺血管重建机制研究进展

低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)与慢性缺氧有关,导致肺心病甚至死亡。低氧性肺血管收缩和肺血管重建(pulmonary vascular remodeling,PVR)通常认为是HPH的两个阶段,前者更强调早期血管收缩,而PVR才是造成血管舒张药无效的主要原因。既往认为PVR是炎症反应导致,但目前更强调多方面、多因子的共同结果。文章主要从细胞因子、氧化应激、细胞内外离子及细胞自噬和凋亡等在HPH进程中的作用出发,介绍目前对HPH治疗的研究进展,提出未来研究方向的猜想。作为一种不可逆的致死性疾病,肺动脉高压(pulmonary arterial hypertension,PAH)一直是当下肺移植相关研究的热点问题,但PAH类型多,且不同类型的PAH形成机制各不相同。文章综述了HPH的PVR形成机制及对应治疗方案。     

Pulmonary vascular resistance determines mortality in end‐stage renal disease patients with pulmonary hypertension

The multifactorial etiology of pulmonary hypertension (PH) in end‐stage renal disease (ESRD) includes patients with and without elevated pulmonary vascular resistance (PVR). We explored the prognostic implication of this distinction by evaluating pretransplant ESRD patients who underwent right heart catheterization and echocardiography. Demographics, clinical data, and test results were analyzed. All‐cause mortality data were obtained. Median follow‐up was 4 years. Of the 150 patients evaluated, echocardiography identified 99 patients (66%) with estimated pulmonary artery (PA) systolic pressure > 36 mm Hg, which correlated poorly with mortality (HR = 1.28, 95% CI 0.72‐2.27, P = .387). Right heart catheterization identified 88 (59%) patients with mean PA pressure ≥ 25 mm Hg. Of these, 70 had PVR ≤ 3 Wood units and 18 had PVR > 3 Wood units. Survival analysis demonstrated a significant prognostic effect of an elevated PVR in patients with high mean PA pressures (HR = 2.26, 95% CI 1.07‐4.77, P = .03), while patients with high mean PA pressure and normal PVR had equivalent survival to those with normal PA pressure. Despite the high prevalence of PH in ESRD patients, elevated PVR is uncommon and is a determinant of prognosis in patients with PH. Patients with normal PVR had survival equivalent to those with normal PA pressures.     

Combined liver and (heart-)lung transplantation in liver transplant candidates with refractory portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension (PPHT) has a prevalence of 5-10% in liver transplantation (LiTx) candidates. Mild PPHT is reversible with LiTx, but more severe PPHT is a contraindication to LiTx given the high intraoperative mortality due to heart failure. Prostacyclin can reduce PPHT to a level at which LiTx can be performed. In patients refractory to that treatment, combined (heart-)lung-LiTx is the only life-saving option. METHODS: We report two cases of (heart-)lung-LiTx in patients with refractory severe PPHT. RESULTS: Patient 1, a 52-year-old female with viral cirrhosis and severe refractory PPHT, received a double-lung Tx followed by LiTx. After liver reperfusion, fatal heart failure occurred. Patient 2, a 42-year-old male with viral hepatitis and congenital liver fibrosis, also suffered from severe refractory PPHT. He successfully received an en bloc heart-lung Tx followed by LiTx. The rationale to replace the heart was an anticipated risk of intraoperative right heart failure after liver reperfusion and the technical ease of heart-lung versus double-lung Tx. CONCLUSION: Severe refractory PPHT is a fatal condition seen as a contraindication to LiTx. This condition can be treated by replacing thoracal organs in addition to the liver. Additional evidence via development of a registry is required to further support application of liver-(heart-)lung Tx in patients with severe refractory PPHT.     

Rapidly progressive pulmonary artery hypertension and end-stage liver disease

Pulmonary hypertension is a recognized but unusual complication of liver disease. It can complicate the perioperative course of liver transplantation. Mild to moderate pulmonary hypertension is generally well tolerated during the procedure and does not appear to contribute to mortality.
Since the pulmonary vascular disease may progress rapidly, it may have advanced to the point of irreversibility at the time of surgery. So, patients with known moderate pulmonary hypertension should have pulmonary arterial catheterisation immediately prior to transplantation. If pulmonary artery hypertension has become severe, then a preoperative trial of vasodilators is warranted. If this fails, the procedure should be cancelled.
We present a patient with alcoholic liver cirrhosis in whom a rapidly progressive pulmonary hypertension made liver transplantation impossible.     

Cardiac diseases among liver transplant candidates

Improvements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post‐LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. As no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work‐up.     

Pulmonary hypertension: considerations in the liver transplant candidate

Pulmonary hypertension is a potentially lethal complication of end-stage liver disease with a prevalence of 2%. In the setting of liver transplantation, the prevalence may be as high as 12%. Given the potential importance of this syndrome to the transplantation community, the purpose of this review is to summarize the current state of understanding of portopulmonary hypertension and to suggest potential management strategies for (1) liver transplant candidates with suspected pulmonary hypertension and (2) intraoperative pulmonary hypertension following liver allograft reperfusion.     

Liver transplantation for pulmonary vascular complications of pediatric end-stage liver disease

Purpose

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are poorly understood pulmonary complications of end-stage liver disease (ESLD). We present a case series of children with HPS and PPH.

Methods

After institutional review board approval, query of our medical database identified children 0 to 18 years of age with ESLD diagnosed with HPS or PPH. Data were collected via chart review.

Results

We identified 7 children with either HPS (n = 5) or PPH (n = 2). Patients with HPS presented with progressive dyspnea over a mean of 7 months (range, 4-12 months) at a mean of 13 years (range, 5-17 years) of age. Pulmonary shunting by albumin perfusion scan averaged 41% (range, 20%-66%) with an initial mean resting Spo₂ of 88% (range, 84%-94%) and mean Spo₂ during exertion of 79% (range, 60%-89%). Four patients required supplemental O₂ and, upon United Network for Organ Sharing (UNOS) appeal, received pediatric model for ESLD (or Child-Pugh) score exceptions, enabling them to undergo orthotopic liver transplant (OLT) within 1-2 months. The fifth patient was initially rejected by the UNOS regional review board, but 6 months of worsening hypoxemia led to OLT 2 months after successful UNOS appeal. All patients with HPS undergoing OLT experienced complete resolution of hypoxemia within 8 months. Both children with PPH were treated with intravenous epoprostenol, which lowered or stabilized mean pulmonary artery pressure and bridged them to OLT within 7 months of listing. Overall, there were no pulmonary complications; however, 1 patient with PPH expired shortly after OLT. The remaining patients are alive at a median follow-up of 27 months (range, 6-96 months).

Conclusion

Hepatopulmonary syndrome and PPH are uncommon complications of ESLD in children. Epoprostenol can bridge PPH patients to OLT. OLT leads to rapid resolution of HPS and PPH and currently represents the only successful treatment for these children.     

Myocardial perfusion imaging is an effective screening test for coronary artery disease in liver transplant candidates

A reliable screening test for coronary artery disease (CAD) in liver transplant (LT) candidates with end‐stage liver disease is essential because a high percentage of perioperative mortality and morbidity is CAD‐related. In this study, the effectiveness of myocardial perfusion imaging (MPI) for identification of significant CAD in LT candidates was evaluated. Records of 244 patients meeting criteria for MPI were evaluated: 74 met inclusion criteria; 40 had a positive MPI and cardiology follow‐up; 27 had a negative MPI and underwent LT; and seven had a negative MPI and then had coronary angiography or a significant cardiac event. A selective MPI interpretation strategy was established where MPI‐positive patients were divided into high, intermediate, and low CAD risk groups. The overall incidence of CAD in this study population was 5.1% and our strategy resulted in PPV 20%, NPV 94%, sensitivity 80%, and specificity 50% for categorizing CAD risk. When applied only to the subset of patients categorized as high CAD risk, the strategy was more effective, with PPV 67%, NPV 97%, sensitivity 80%, and specificity 94%. We determined that renal dysfunction was an independent predictive factor for CAD (p < 0.0001, odds ratio = 8.1), and grades of coronary occlusion correlated significantly with chronic renal dysfunction (p = 0.0079).     

Screening colonoscopy in liver transplant candidates: risks and findings

The indication for mandatory screening colonoscopies in liver transplant candidates is controversial. Since the introduction of MELD‐based allocation, patients with advanced liver disease and often severe comorbidities are prioritized for liver transplantation (LT). This study evaluated safety and outcome of colonoscopy in this high‐risk patient group. During a two‐yr period, we performed 243 colonoscopies in potential LT candidates. Endoscopic findings were registered in a standardized form, and correlations with biochemical or clinical parameters were analyzed using Mann–Whitney U‐test and chi‐square test. Only 57 patients (23.5%) had an endoscopically normal colon. Main findings were polyps (45.7%), hypertensive colopathy (24.3%), diverticulosis (21%), rectal varices (19.8%), and hemorrhoids (13.6%). In 21% of all patients, the removed polyps were diagnosed as adenomas. The prevalence of neoplastic polyps increased significantly with age: 13.6% (patients <50 yr) vs. 25% (patients ≥50 yr) (p = 0.03). Advanced neoplasia was found only in patients older than 40 yr. No major complications were observed; post‐interventional hemorrhage was observed in 1.7% and controlled by clipping or injection therapy. In conclusion, lower gastrointestinal endoscopy is safe and effective in LT candidates. Due to the age dependency of neoplastic polyps, a screening colonoscopy should be performed in LT candidates older than 40 yr or with symptoms or additional risk factors.