Sildenafil Monotherapy to Treat Portopulmonary Hypertension Before Liver Transplant

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.     

Successful pulmonary thromboendarterectomy for right atrial thrombosis in a heart transplant recipient: a case report

Acute massive or submassive pulmonary embolism is a life-threatening condition with a poor prognosis. It causes sudden hemodynamic deterioration and warrants immediate surgery. We report the case of a 41-year-old male heart transplant recipient who had not been treated prophylactically for thrombosis, who was referred to our center because of exertional dyspnea after immobilization owing to an injury in one of his legs. Transesophageal echocardiography revealed a large, mobile, right atrial mass originating from a pacemaker lead. Furthermore, contrast-enhanced computed tomography scanning of the chest revealed multiple pulmonary emboli resulting in subtotal occlusion of both pulmonary arteries. Although typically reserved for patients with chronic thromboembolic pulmonary hypertension, surgical thromboendarterectomy was successfully performed. Six months after discharge, the patient is well and has a New York Heart Association class 1 rating. This is the first report of a successful pulmonary thromboendarterectomy in a heart transplant recipient.     

Role of sildenafil in acute posttransplant right ventricular dysfunction: successful experience in 13 consecutive patients

BACKGROUND: Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. METHODS: Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. RESULTS: Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. CONCLUSION: Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.     

Amrinone versus conventional therapy in pulmonary hypertensive patients awaiting cardiac transplantation

Pulmonary hypertension is associated with an increased perioperative mortality for orthotopic heart transplantation. A transpulmonary gradient greater than 15 mm Hg or a pulmonary vascular resistance greater than 5 Woods units increases mortality secondary to right heart failure. This study compares amrinone with conventional therapy in 38 transplant candidates with pulmonary hypertension. All patients had elevated transpulmonary gradient, pulmonary vascular resistance, or both. Group 1 (n = 21) received prolonged continuous intravenous amrinone therapy, whereas group 2 (n = 16) received high-dose oral diuretics, digitalis, and captopril. Both groups 1 and 2 had decreased pulmonary hypertension, transpulmonary gradient, and pulmonary vascular resistance. However, amrinone was more effective, with a 86% response rate versus 63% response for conventional therapy. Survival awaiting transplantation was significantly higher in group 1 (20 of 22, 91%) than in group 2 (10 of 16, 63%). Although both groups 1 and 2 had significantly decreased pulmonary vascular resistance, only group 2 had significantly decreased systemic vascular resistance. Comparison of pulmonary vascular resistance after therapy showed that the response in group 1 (amrinone) was significantly lower than the response in group 2 (conventional therapy), suggesting that amrinone may function as a direct vasodilator of the pulmonary vasculature. There were no operative deaths or episodes of perioperative right heart failure in either group. Amrinone appears to be more effective and safe than conventional therapy in the treatment of prospective heart transplant candidates with pulmonary hypertension.     

Inhaled nitric oxide through a noninvasive ventilation device to assess reversibility of pulmonary hypertension in selecting recipients for heart transplant

INTRODUCTION: Pulmonary hypertension (PHT) is an independent risk factor for right ventricular failure and death after heart transplant. Nitric oxide (NO) is a powerful and selective vasodilator, indicated in this scenario, but its response is unpredictable. Thus, it should be assessed prior to the intervention. However, preoperative assessment has not been widespread due to its difficulties and risks. OBJECTIVE: We describe herein a pulmonary vasodilatory test with NO administered through a noninvasive ventilation (NIMV) device. We also assessed the effect of NO in patients with severe PHT owing to cardiac disease. Assessment of the utility of the test to select patients for heart transplant. METHODS: We enrolled 19 patients with severe PHT for a preoperative assessment for heart transplant. Thresholds used were as follows: systolic pulmonary arterial pressure (SPAP) > or =65 mm Hg, transpulmonary gradient (TPG) > or =15 mm Hg, and pulmonary vascular resistance (PVR) > or =4.5 Wood units (WU). NO was administered through a modified noninvasive ventilation device. Cardiac output and pulmonary pressures were measured simultaneously by right heart catheterization. RESULTS: All patients agreed to be enrolled in the test. No difficulties, interruptions, or severe complications happened in any case. Basal and NO average measured values were SPAP (74.16 and 57.95 mm Hg), PVR (7.5 and 3.7 WU), and TPG (23.25 and 12.58 mm Hg). The differences were significant (P < .05) for all three tests. We consider acceptable for heart transplant a response that reduces PHT to a moderate grade. Using these criteria 14 patients were accepted and 11 underwent heart transplant. Two deaths in the postoperative period were both secondary to mediastinal bleeding and not related to right ventricular failure. CONCLUSIONS: A pulmonary vasodilatory test with NO administered through a NIMV device was feasible and useful to select suitable heart transplant recipients with severe pulmonary hypertension.     

A Model of Unilateral Pulmonary Lobar Transplantation

Unilateral lung transplantation has become an accepted treatment for patients with end-stage pulmonary disease. Donor shortage, however, is a major limitation, with up to 87% of patients dying of their pulmonary disease while awaiting transplantation. This is especially true in neonatal and pediatric patient populations. The use of organ segments from cadaveric or living donors may provide a solution. The purpose of this study, therefore, was to evaluate the function and hemodynamic response to pulmonary lobar transplantation using a swire model. Five transplants were performed for acute study, while 10 were performed for 6-week survival. The left lower lobe was harvested from a 70- to 75-kg donor animal. The lobe was then transplanted into a 20 to 25-kg recipient following left pneumonectomy. Graft function was determined by pulmonary arterial and venous blood gas analysis. Cardiac output, pulmonary pressure, and pulmonary vascular resistance were measured under two experimental conditions: (I) baseline and (2) with the right pulmonary artery occluded, forcing the entire cardiac output through the lobar graft. All grafts showed excellent acute and long-term function with regard to gas exchange. The lobar grafts, however, were characterized by high pulmonary vascular resistance both acutely and 6 weeks post-transplant. Contralateral pulmonary after) occlusion resulted in hemodynamic instability and right heart failure. No animal was able to be solely supported by the lobar transplant for more than one hour. Thesis results have prompted a bilateral lobar transplant model and current studies are in progress.     

Recombinant factor VIIa for life-threatening bleeding in high-risk cardiac surgery despite full-dose aprotinin

We report the case of an orthotopic heart transplant in a patient with multiple previous cardiac surgeries. The case was prolonged and complicated by severe coagulopathy and bleeding despite the use of full-dose aprotinin throughout. Bleeding was not controlled after 30 U of platelets, 20 U of fresh frozen plasma, and 10 U of cryoprecipitate. However, after the administration of recombinant factor VIIa 90 microg/kg, the rate of bleeding slowed dramatically and no further factor replacement was required. There was no evidence of unwanted clot formation within the newly transplanted heart or around the intraaortic balloon pump that remained in situ for 72 h postoperatively. With the combined risks of coagulopathy and bleeding as well as acute right ventricular failure with increases in pulmonary vascular resistance, the re-do sternotomy for heart transplant seems to be an ideal situation in which to consider the use of recombinant factor VIIa.     

Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.     

Is there a correlation between brain naturietic peptide levels and echocardiographic and hemodynamic parameters in heart transplant patients?

BACKGROUND: Brain naturietic peptide (BNP) elevations have been reported in heart transplant patients both at baseline and during rejection. An association between BNP levels and certain echocardiographic and hemodynamic abnormalities has also been found in nontransplanted heart disease patients. We sought to determine whether BNP values were correlated with echocardiographic and hemodynamic parameters among a large cohort of heart transplant patients. MATERIALS AND METHODS: We studied 71 consecutive heart transplant patients, excluding combined grafts, retransplants, and pediatric cases. We performed 488 BNP determinations during catheterization and within 48 hours of echocardiography. Hemodynamic parameters included mean pulmonary artery pressure, right ventricular systolic and diastolic pressures. Doppler echocardiography parameters were wall thickness, ventricular mass, left and right ventricular end-diastolic and end-systolic diameters, isovolumic relaxation time, and mitral flow deceleration time. RESULTS: We observed significant correlations between BNP values and left ventricular size, ventricular mass, and a restrictive filling pattern. BNP levels were also significantly correlated with right ventricular size, mean pulmonary artery pressure, and right ventricular diastolic and end-diastolic pressures. CONCLUSIONS: In heart transplant patients, BNP levels positively correlated with ventricular diameters and a restrictive filling pattern. An increase in right ventricle and pulmonary artery pressures was associated with elevated BNP values.     

Lung Transplant After a Heart Transplant: A Case Report

A heart-lung transplant is considered in patients with end-stage heart and lung disease. However, there is no report of a patient receiving a staged heart transplant followed by a lung transplant. Our case report describes a successful left single lung transplant for idiopathic pulmonary fibrosis 6 years after a heart transplant. This case illustrates that this approach can avoid significantly increased wait time until transplant, and it shows that early interstitial lung disease may not be a contraindication for the heart transplant.     

Treatment of a case of acute right heart failure by inhalation of iloprost, a long-acting prostacyclin analogue

Perioperative acute right heart failure after orthotopic heart transplantation contributes significantly to morbidity and mortality. Vasodilators administered intravenously may decrease pulmonary vascular resistance, but also affect systemic circulation. A decrease of mean arterial pressure will result in reduced right coronary blood flow and deterioration of right ventricular performance. Vasodilators administered by inhalation, i.e. nitric oxide and prostacyclin, are attractive due to a more selective effect on the pulmonary circulation. This is the first report on the use of aerosolized iloprost, a long-acting prostacyclin analogue, applied for treatment of postoperative right heart failure in cardiac transplantation. After uneventful surgery, a heart transplant recipient was extubated on the first postoperative day and exhibited right heart failure on the following day. Standard treatment did not resolve this clinical problem sufficiently. A trial with inhalation of iloprost (16 microg per inhalation cycle, applied six times per day) was initiated. Iloprost inhalation resulted in a sufficient decrease of pulmonary vascular resistance (-23.5%), while cardiac index (+24.0%) and mixed venous saturation (+9.0%) increased. No profound effect on the systemic vascular resistance was observed (-2.8%). Iloprost inhalation may be an effective alternative to nitric oxide in the intensive care management of acute right heart failure after orthotopic heart transplantation. Due to the prolonged effect on the pulmonary vascular resistance, iloprost is especially useful for extubated patients.     

An unusual case of Aspergillus endocarditis in a kidney transplant recipient

The incidence of aspergillosis in kidney transplant recipients is low and most commonly occurs in the early posttransplantation period. We report an unusual case of a 52-year-old female patient with Aspergillus endocarditis as a late complication after kidney transplantation, presumably spread from a necrosis in the gut, associated with previous cytomegalovirus colitis. As complications, the patient experienced septic embolization into the coronary and pulmonary arteries, and an infarction of the right parietal cortex and insula. The patient died as a result of global heart failure after a 10-day course of antimycotic therapy with amphotericin B plus 5-flucytosine during surgical valve replacement.     

Survival benefits of heart and lung transplantation.

OBJECTIVE: Heart and lung transplantation has gained acceptance as therapy for end-stage cardiac and pulmonary failure. The early and intermediate survival benefits of one center's 10-year experience with 177 patients undergoing thoracic transplantation were examined. SUMMARY BACKGROUND DATA: As experience in cardiac and pulmonary transplantation has increased, improvements in patient selection, organ preservation, preoperative support, and perioperative care have significantly reduced the early threats to patient survival. Graft dysfunction due to chronic rejection appears to be the main risk for longer-term survival, and data compiled by the United Network for Organ Sharing (UNOS) indicate a 70% 5-year survival for heart transplants and a 50% 5-year survival for lung transplant recipients. METHODS: The medical records of 120 heart recipients, 52 lung transplant recipients, and 5 heart-lung recipients were reviewed. Cumulative survival estimates were made using Kaplan-Meier analysis. The etiologies of operative and long-term mortality in each transplant population were identified. A comparison of long-term survival after heart transplantation versus coronary revascularization in a group of patients with ischemic cardiomyopathy was performed. RESULTS: Operative mortality in both the cardiac and pulmonary transplant recipients was 8%. From 1990 to 1995, 70 consecutive adult cardiac transplant procedures were performed without an operative mortality. Three of five patients survived heart-lung transplantation. The extended actuarial survival rate at 5 years was 80% for the cardiac transplant recipients. The 2-year actuarial survival rate for the lung transplant recipients was 88%. Graft dysfunction was the most common cause of operative mortality in the heart transplant group whereas infection was responsible for most of the operative mortality after lung transplantation. CONCLUSIONS: Cardiac and pulmonary transplantation can be applied to morbidly ill patients with excellent operative and intermediate-term survival.     

Implantation of the Biomedicus centrifugal pump in post-transplant right heart failure

BACKGROUND: Right heart failure after heart transplantation represents a life-threatening complication. When conventional therapy including NO-inhalation fails the only choice to reach sufficient haemodynamic conditions may be the implantation of a right ventricular support system. METHODS: In all cases the Biomedicus centrifugal pump was implanted by cannulation of the right atrium and pulmonary artery. RESULTS: Since March 1989 950 heart transplant procedures were performed at our center. In nine cases (7 male, 2 female, mean age 52 years) implantation of a right ventricular support system was necessary because of deterioration of right ventricular function. The implantation was carried out in 7 cases immediately after transplantation, in 2 cases after 2 days. The support time ranged from 4-348 hours. Six patients could be weaned, 2 patients underwent retransplantation and died and 1 patient died on the support system. Three of the six weaned patients died in the further course because of multiorgan failure. CONCLUSIONS: Mechanical right ventricular support is often the only therapeutical tool to reach adequate haemodynamic conditions in post-transplant right heart failure. The Biomedicus centrifugal pump provides good conditions in these cases. Weaning is often possible after short-term support. The mortality rate is determined by multiorgan failure in immuno-suppressed patients. Retransplantation seems not to be successful despite maximal treatment.     

Normalization of high pulmonary vascular resistance with LVAD support in heart transplantation candidates.

OBJECTIVE: Pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) lead to poor outcome after heart transplantation due to postoperative failure of the non-conditioned right ventricle. The role of continuous flow left ventricular assist device (LVAD) support in the reduction of elevated PVR was evaluated in a series of clinical implants. METHODS: Among 17 patients with terminal heart failure receiving a MicroMed DeBakey LVAD as bridge to transplant, there were six patients with pulmonary hypertension (mean systolic PAP 47 mmHg) and high PVR (398 dynes/cm5), previously not considered suitable for heart transplantation, who underwent serial right heart catheters during their LVAD support period. RESULTS: In these patients mean systolic pulmonary pressure dropped to 29 mmHg and PVR decreased to a mean 167 dynes/cm5 under LVAD support. Clinical improvement was significant in all patients. Four patients were successfully transplanted without major postoperative difficulties (mean duration 130 days support) and all are doing well to date. Post-transplant-PVR remained in the normal range in all transplanted patients. CONCLUSIONS: Elevated PVR and severe PH were both previously considered as contraindication for heart transplantation. A period of LVAD pumping leads to a progressive decrease of PVR and normalization of pulmonary pressures, making these patients amenable for heart transplantation. LVAD as bridge to heart transplantation is safe and highly beneficial for terminal heart failure patients with severe PH.     

Collective review: perioperative uses of inhaled nitric oxide in adults

Pulmonary arterial hypertension and hypoxemia constitute a significant cause of postoperative right heart failure and mortality. Timely administration of inhaled nitric oxide (iNO) can improve hemodynamic parameters and oxygenation in patients undergoing heart and/or lung transplantation and various high-risk cardiac procedures involving coronary artery bypass grafting and/or left ventricular assist device placement. As a diagnostic tool, iNO can be used to identify heart transplant recipients at high risk of right ventricular failure and patients with primary pulmonary hypertension who may benefit from vasodilator therapy. In addition to its role as a potent and selective pulmonary vasodilator, iNO is a useful intraoperative adjunct in adult cardiac surgery patients that may reduce the need for right ventricular assist device placement. This review focuses on the multiple clinical applications of iNO in perioperative patient care.     

Successful treatment of pulmonary hypertension with inhaled nitric oxide after pulmonary embolectomy

Inhaled nitric oxide is an agent known to reduce pulmonary vascular resistance and prevent right heart failure. Pulmonary embolism is frequently followed by right heart failure and cardiogenic shock. Although successful treatment of patients with right ventricular failure caused by pulmonary embolism has been reported, clinical use of inhaled nitric oxide as an adjunct to surgical treatment is not in widespread use. We present a case of a 69-year-old woman with massive pulmonary embolism followed by right ventricular failure. After emergency operation, weaning from ventilation was prolonged. Pulmonary hypertension was decreased with low-dose inhaled nitric oxide, although pulmonary gas exchange did not improve. The patient was weaned successfully from ventilation 52 hours after operation and recovered completely. In a follow-up examination after 9 months, the patient is in healthy constitution with good cardiopulmonary function.     

Effect of a reduced donor heart right ventricular distensibility on post-heart transplant haemodynamics

Open in a separate window OBJECTIVESThis study aimed to investigate the characteristics of a reduced right ventricular distensibility after heart transplant.METHODSThis 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.RESULTSOf 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.CONCLUSIONSReduced 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.     

Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation—a preliminary study

Objectives: Elevated pulmonary vascular resistance (PVR) unresponsive to pharmacological intervention is a major limitation in heart transplantation (HTX). The post-operative course of these patients is associated with an increased risk of life-threatening right heart failure. We evaluated the efficiency of an implantable left ventricular assist device (LVAD) to decrease PVR by unloading the left ventricle and to lower the risk of later orthotopic HTX. Methods: Six patients with end-stage heart failure (NYHA class IV) and ’fixed‘ pulmonary hypertension (PVR 5.7±0.7, range 4.4–6.5 Wood units) were analyzed. Despite maximal pharmacological intervention at initial evaluation (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a Novacor, and one patient a Jarvik 2000. Results: All patients survived the LVAD implantation, four patients could be discharged from hospital. Cardiac index and pulmonary artery pressure values returned to normal during the early post-operative phase. After a mean support time of 191±86 days PVR had fallen to 2.0±1.2 (range 0.8–3.6) Wood units. All patients could be bridged to transplantation, one patient died 3 months after transplant, five patients are still alive after a mean follow-up of 16.2±10.5 months. Conclusions: Mechanical support using an implantable LVAD is a very efficient approach with an acceptable risk to treat severe pulmonary hypertension in end-stage heart failure patients before HTX. Adequate reduction of PVR can be expected within 3–6 months. Subsequent HTX is associated with a good outcome.     

Early diagnosis and follow-up by echocardiography of acquired cor triatriatum after orthotopic heart transplantation.

Acquired cor triatriatum in a heart transplant recipient, secondary to a prominent left atrial suture line and torsion of the atria, was diagnosed immediately after cardiopulmonary bypass by transesophageal echocardiography. The patient was followed with serial echocardiograms and right heart catheterizations, showing resolution of the obstruction.