Nitric oxide inhalation in the treatment of primary graft failure following heart transplantation.

BACKGROUND: Primary graft failure from right or left ventricular insufficiency remains a serious cause of early death following heart transplantation. Inhaled nitric oxide (NO) is a potent pulmonary vasodilator that could decrease pulmonary pressure and improve right ventricular function. METHODS: Two cases of early graft failure following orthotopic heart transplantation were treated with NO inhalation. The treatment consisted of inhalation of 20 ppm of NO, introduced 4 to 6 hours following transplantation, in 2 patients supported with high doses of inotropic agents and vasopressors in addition to the intra-aortic balloon pump. RESULTS: In the first and second cases, NO inhalation resulted in a decrease in pulmonary artery pressure, in a decrease in pulmonary vascular resistance and in an increase in cardiac index. In the second patient, systemic oxygenation improved markedly 30 minutes after initiation of NO. In the 2 patients, NO inhalation, mechanical ventilation and the intra-aortic balloon pump were weaned 4 days following transplantation. CONCLUSION: Primary graft failure from donor ischemic damage, reperfusion injury or pulmonary hypertension remains a serious complication. The use of an intra-aortic balloon pump, inotropic agents and of inhaled NO appears to offer the best support for recovery of donor heart function. Primary graft failure from right or left ventricular insufficiency remains a serious cause of early mortality following heart transplantation. Ischemic damage of donor heart, reperfusion injury or pulmonary hypertension are the main causes of early graft failure. Although the cause is multifactorial, treatment of primary organ failure remains difficult with dismal results. The objective of the present study was to review the result of 2 patients with donor right heart failure following heart transplantation treated with inhaled nitric oxide (NO).     

Extracorporeal membrane oxygenation is superior to right ventricular assist device for acute right ventricular failure after heart transplantation

Background

Acute right ventricular failure after heart transplantation is a life-threatening condition, and sometimes the use of mechanical circulatory support is inevitable. The aim of this retrospective study was to investigate the effectiveness of two different mechanical circulatory support systems for this indication.

Methods

From 1984 to 2003, 28 heart transplant recipients exhibited right ventricular failure resistant to drug therapy. Right ventricular assist device (n = 15) or extracorporeal membrane oxygenation (n = 13) was implanted to support the failing heart.

Results

Overall in-hospital survival was 43%. In the right ventricular assist device group, only 2 patients (13%) could be weaned from mechanical circulatory support compared with 10 patients (77%) in the extracorporeal membrane oxygenation group (p = 0.001). Retransplantation was necessary in 6 patients in the right ventricular assist device group and in 1 patient in the extracorporeal membrane oxygenation group (p = 0.049). There was no difference in patient survival between groups, but graft survival was significantly better in the extracorporeal membrane oxygenation group (p = 0.005).

Conclusions

In view of these results, extracorporeal membrane oxygenation seems to be the better option as mechanical circulatory support for right ventricular failure in heart transplantation.     

A new right ventricular assist device for right ventricular support.

Right ventricular support by mechanical devices for postcardiotomy right heart failure is still associated with a high mortality. We report on the first use of a new paracardiac microaxial blood pump for postcardiotomy right heart failure in two patients undergoing emergency coronary artery bypass grafting (the first patient for a myocardial infarction complicated by a left ventricular wall rupture, the second patient for a dissection of the right coronary artery after an interventional procedure).     

Right ventricular support after implantation of a Novacor Left Ventricular Assist Device

The objective was to determine which factors might help to predict the need for mechanical right ventricular support following insertion of a left ventricular assist device (LVAD). A retrospective analysis was performed on 24 patients with cardiomyopathies who had insertion of a LVAD as a bridge to heart transplantation at Presbyterian University Hospital during the period 1987 to 1991. Group 1 consisted of 18 patients who could be adequately supported with the LVAD alone, while Group 2 consisted of 6 patients who required additional support with a right ventricular assist device. Group 2 exhibited longer periods of hypotension on cardiopulmonary bypass, increased inotropic support and decreased right ventricular ejection fraction at time of chest closure post-LVAD.     

Right ventricular dynamic cardiomyoplasty: an experimental model

The effectiveness of dynamic cardiomyoplasty as a means of haemodynamic support in heart failure remains controversial. We have undertaken a study of right ventricular dynamic cardiomyoplasty in sheep using intravenous propranolol to provoke heart failure. Muscle conditioning was performed with cardiomyostimulators following a previously established protocol. We performed multiple invasive measurements of haemodynamic parameters including arterial blood pressure, cardiac output, pulmonary artery capillary wedge pressure, right ventricular dp/dt and end diastolic pressures. These were performed before induction of heart failure, after induction of heart failure, and with pacing of the cardiomyoplasty flap in established heart failure. Our results confirm that we were able to establish significant heart failure and that subsequent pacing of the conditioned muscle flap was able to return cardiac output and right ventricular function to their pre-failure control levels.     

Postoperative acute refractory right ventricular failure: incidence, pathogenesis, management and prognosis

Isolated acute refractory right ventricular failure is extremely uncommon. There are greater prospects of seeing a right dominant biventricular failure, as the two ventricular chambers are contiguous. The overall clinical spectrum is determined by the relative ischemic involvement of the right or left ventricle. The postoperative acute refractory right ventricular failure that develops after cardiotomy, heart transplant, or during a left ventricular assist device support, may have somewhat dissimilar elements of origin, but the resultant clinical picture and the management are essentially similar. In this collective review, the authors have summarized the incidence, pathogenesis, management and prognosis of postoperative acute refractory right ventricular failure, in adult cardiac surgical practice. The incidence of post-cardiotomy acute refractory right ventricular failure ranges from 0.04 to 0.1%. Acute refractory right ventricular failure has also been reported in 2-3% patients after a heart transplant and in almost 20-30% patients who receive a left ventricular assist device support. The main contributor to this problem is a disproportionate ischemic involvement of the right ventricle. Other pertinent contributors to this problem are pulmonary hypertension and an altered interventricular balance. The latter component is predominant in recipients of a left ventricular assist device support. Postoperative acute refractory right ventricular failure has been successfully managed with conventional pulmonary vasodilators, mechanical support with a pulmonary artery balloon pump, a right ventricular assist device, or cavopulmonary diversion. Unfortunately, the reported initial salvage rate is only 25-30%. This problem is often underestimated. Support measures are often started late or terminated prematurely. These factors have contributed to a poor initial salvage rate in this group of patients.     

Use of the Heartmate 3 for biventricular support as a bridge to heart transplant‐first US implant

Right ventricular failure continues to be the Achilles heel in the management of heart failure patients. Traditionally, either high doses of inotropes and inhaled nitric oxide or jerry‐rigged temporary mechanical devices have been used to support failing right ventricles. No durable implantable right ventricular assist device has been developed to address this long‐standing concern. Because of this vacuum of innovation, surgeons have started using the third‐generation LVADs to support the right ventricle. The HeartMate 3 (Abbott) LVAD is a safe and effective therapy for the management of biventricular failure.     

Mechanical Support for Postcardiotomy Heart Failure

Cardiac failure remains a life-threatening complication for certain patients undergoing intracardiac repair. Despite improvements in surgical techniques, methods of myocardial protection, and postoperative care, patients are frequently at risk to develop postoperative low output syndrome. Approximately 1% of cardiac surgical patients cannot be weaned from extracorporeal circulation in spite of adequate volume loading, the use of inotropic support, and initiation of intraaortic balloon pumping. In these cases, ventricular assist devices (VAD) can mechanically aid the failing heart and reverse the low output state. The concept of mechanical support for the failing left ventricle was first proposed by Clauss et al. in 1961. By 1968, Kantrowitz and associates had developed and refined the first intraaortic balloon pump (IABP). Through the efforts of Moulopolous and others, this device evolved into the present-day intraaortic balloon pump (IABP). Clinical evidence for the efficacy of left ventricular assist devices (LVAD) remained questionable until 1980, when the National Heart, Blood and Lung Institute evaluated short-term LVADs by comparing various types of mechanical aids. This report focused attention primarily on the failing left ventricle (LV). As the use of inotropic support, intraaortic balloon pumping, and LVADs improved, a small group of patients emerged who could not be separated from extracorporeal circulation due to a failing right ventricle. The failing right ventricle emerged as a unique clinical entity similar to postcardiotomy left ventricular failure that also benefited from mechanical cardiac assistance. Current therapy at major centers incorporating mechanical assist devices is based on the premise that the low output state will allow the failing heart to recover from a reversible injury. The frequent occurrence of postcardiotomy ischemia may be due to several factors such as poor myocardial protection, overdistension of the LV, emboli, coronary spasm or technical problems. Whatever the etiology, the end product of cardiac failure is a demand for oxygen consumption that cannot be met, thus leading to cardiac demise.     

Mechanical support of the circulation followed by cardiac transplantation

Improvements in both mechanical circulatory support devices and immune therapy promise a wider use of sequential mechanical support as a bridge to orthotopic cardiac transplantation. The intra-aortic balloon pump, the left and right ventricular assist pumps, and the pneumatic artificial heart represent the range of devices capable of keeping a patient alive who is awaiting a donor organ. The major difficulty in using circulatory support devices is infection, which is caused by their required percutaneous tubes. We report here our experiences with mechanical circulatory support devices as a bridge to cardiac transplantation. In a series of 31 consecutive transplant procedures, six patients have required preoperative mechanical circulatory support. The intra-aortic balloon pump was used in two patients for 2 and 14 days, respectively, before transplantation. Both patients are well 10 and 11 months after the transplant procedure. Two patients required the left ventricular assist device for 11 and 21 days and are alive 3 weeks and 8 months, respectively, after transplantation. One patient was supported by the pneumatic artificial heart for 10 days before a donor heart became available but died of septic shock 17 days after transplantation. A second patient received a pneumatic artificial heart 7 days after transplantation when the heart transplant failed. He has been in stable condition for 45 days but is recovering from renal failure. Our early experiences indicate that either partial or total mechanical support as a bridge to transplantation is successful if overwhelming sepsis or renal failure can be avoided.     

Ventricular assist support of the failing heart after surgery with extracorporeal circulation

OBJECTIVE: To communicate our experience implanting ventricular assist devices; we report the incidence of refractory heart failure after extracorporeal circulatory support and discuss clinical course after support. PATIENTS AND METHOD: Retrospective study of 14 cases of ventricular assistance required when refractory heart failure developed after extracorporeal circulation. The patients were 10 males and 4 females aged between 12 and 70 years. Four underwent coronary revascularization, 2 required valve replacement, and 8 received heart transplants. Two left, 2 right and 6 bilateral ventricular assist devices were implanted. RESULTS: The incidence of refractory heart failure after extracorporeal mechanical circulation requiring ventricular assist devices among our patients was 0.48%, with left ventricular failure occurring in 21.42%, right ventricular failure in 42.85% and biventricular failure in 35.71%.The main complications were infection, renal insufficiency, coagulation disorder, hemorrhage with repeated surgery. One patient received a second transplant. The device was successfully withdrawn from 35.7% of the patients. Survival upon discharge was 7.1%. CONCLUSION: Refractory heart failure after extracorporeal circulation is a life-threatening event requiring rapid response and resolution. The decision to implant a ventricular assist device is a difficult one, requiring immediate assessment of the causes of heart failure, its reversibility and the possibility of performing a heart transplant. The study of large series of patients experiencing this event and implanted with ventricular assist devices would facilitate decision making.     

Mechanical circulatory support for myocarditis: how much recovery should occur before device removal?

A 12-year-old girl with presumed myocarditis was supported with right and left ventricular assist devices for 68 days before device removal. During this time, the patient underwent echocardiography and right heart catheterization for evaluation of cardiac recovery. This case report serves as the basis for a discussion of criteria for deciding when to terminate mechanical circulatory support in a patient with recovery after acute myocarditis.     

Temporary right heart assist: a minimally invasive approach

A surgical method for the implantation of a mechanical right ventricular assist device which avoids resternotomy/thoracotomy and related complications at the time of explantation is presented. In order to support the failing right heart, a Dacron vascular graft was sewn to the pulmonary artery. For venous drainage, a cannula was inserted into the right atrium via the femoral vein. Explantation of the system, after the right heart resumed its function, was accomplished by retracting and compressing the venous cannula in the groin as well as by retracting the arterial cannula from the Dacron vascular graft followed by suturing without opening the chest. Between 2006 and 2011, this system was used in 12 patients. The median duration of right heart support was 10.5 days. Seven patients were successfully weaned from the system, six patients survived. In all cases, explantation was free of complications. The technique described is a safe method to support the right heart and allows explantation without the risks and complications of reopening the thorax.     

Successful Extracorporeal Membrane Oxygenation for Right Heart Failure After Heart Transplantation—2 Case Reports and Literature Review

After heart transplantation (HT), transient right heart failure (RHF) is common. If it does not improve with appropriate medical therapy, we must consider mechanical support. Recently, extracorporeal membrane oxygenation (ECMO) has shown better results than a right ventricular assist device or retransplantation. Two HT patients with hypertrophic cardiomyopathy had cold ischemic times beyond >240 minutes. After HT, their right heart function worsened and was unresponsive to medical therapy. After our application of ECMO, weaning was successful and the patients were discharged without complication. Early application of ECMO for RHF after HT is a good option.     

Mechanical support of the pediatric cardiac patient

Increased understanding of the anatomical nuances of congenital heart defects, improved methods of myocardial preservation, and advances in surgical techniques have led to improved results and need for postoperative mechanical support in patients undergoing congenital heart surgery. However, there remains a small portion of patients with myocardial or pulmonary failure that can can be rescued by intelligent use of mechanical support. The most widely used form of mechanical support is extracorporeal membrane oxygenation (ECMO), which has been adapted for use in congenital heart patients as well as patients with respiratory failure. Recent reports have suggested that ventricular support devices may also be useful in this patient population. A promising new application of mechanical support is for rescue during cardiac arrest; surprisingly good results have been obtained in this obviously moribund group of patients. Future developments in mechanical support include more accurate identification of patients who will benefit from this therapy and technological advances that will provide greater biocompatibility and simplification of the support circuit. Copyright © 2000 by W.B. Saunders Company     

Exposure of circumflex branches in the tilted, beating porcine heart: echocardiographic evidence of right ventricular deformation and the effect of right or left heart bypass.

OBJECTIVE: In off-pump coronary surgery, exposure of posterior vessels via sternotomy causes deterioration of cardiac function. Changes in ventricular geometry, valve competence, and hemodynamics after retraction of the beating heart were studied. Subsequently, the modifying effect of right or left heart bypass was investigated. METHODS: In six 80-kg pigs, an ultrasound probe was attached to the backside of the left ventricle and the heart was fully retracted with a suction tissue stabilizer. Five pigs underwent additional pump support. RESULTS: During retraction, the right ventricle was squeezed between the pericardium and interventricular septum, thereby decreasing its diastolic cross-sectional area by 62% +/- 6% (P <.001) while, concomitantly, right ventricular end-diastolic pressure increased to 165% +/- 19% (P =.004) of basal values. Stroke volume and mean arterial pressure decreased by 29% +/- 6% and 23% +/- 8% (P =.007 and P =.02, respectively). Left ventricular shape became somewhat elliptic without changes in preload pressure, and its diastolic cross-sectional area decreased by 20% +/- 3% (P =.001). All valves were competent. Right heart bypass restored left ventricular cross-sectional area, stroke volume, and mean arterial pressure. In contrast, left heart bypass increased blood pressure only marginally. CONCLUSIONS: Ninety-degree anterior displacement of the beating porcine heart caused primarily right ventricular dysfunction as a result of mechanical interference with diastolic expansion without concurring valvular incompetence. Right heart bypass normalized stroke volume and mean arterial pressure by increasing left ventricular preload; in contrast, left heart bypass failed to restore systemic circulation.     

Clinical experience of mechanical ventricular support with centrifugal pump for severe ventricular failure after open heart surgery

Five adult patients (pts) with age 15-67 (mean 43) received mechanical circulatory support with centrifugal pump (Biomedicus, BP-80, Sarns centrifugal pump) for postcardiotomy profound shock. Three pts underwent left ventricular support (LVS) alone, and the other 2 required biventricular support (BVS). Duration of the LVS ranged from 33 to 240 hours (mean 126 hours) and the right ventricular support 92, 120 hrs. Pump flow rate was 1.1 to 2.5 (mean 1.9) L/min/m2. Sixteen pumps were used and the pump exchange was performed 9 times in five pts and an average perfusion time per pump was 57 hrs. Two of 3 pts with LVS alone survived and one died of multiorgan failure associated with right heart dysfunction. In two pts with BVS, one survived and the other died of persistent low cardiac output early after pump removal. As the complication during mechanical support, bleeding was seen in 3 pts and cerebral infarction in one. Although centrifugal pump has potential limitation in antithrombogenicity and durability, this device provides a simple and effective mechanical circulatory support.     

A Mathematical Model to Evaluate Control Strategies for Mechanical Circulatory Support

Continuous flow ventricular assist devices (VADs) for mechanical circulatory support (MCS) are generally smaller and believed to be more reliable than pulsatile VADs. However, regarding continuous flow, there are concerns about the decreased pulsatility and ventricular unloading. Moreover, pulsatile VADs offer a wider range in control strategies. For this reason, we used a computer model to evaluate whether pulsatile operation of a continuous flow VAD would be more beneficial than the standard constant pump speed. The computer model describes the left and right ventricle with one-fiber heart contraction models, and the systemic, pulmonary, and coronary circulation with lumped parameter hemodynamical models, while the heart rate is regulated with a baroreflex model. With this computer model, both normal and heart failure hemodynamics were simulated. A HeartMate II left ventricular assist device model was connected to this model, and both constant speed and pulsatile support were simulated. Pulsatile support did not solve the decreased pulsatility issue, but it did improve perfusion (cardiac index and coronary flow) and unloading (stroke work and heart rate) compared with constant speed. Also, pulsatile support would be beneficial for developing control strategies, as it offers more options to adjust assist device settings to the patient's needs. Because the mathematical model used in this study can simulate different assist device settings, it can play a valuable role in developing mechanical circulatory support control strategies.     

A novel use of the implantable ventricular assist device for isolated right heart failure

Isolated right heart failure after cardiac surgery is uncommon and the prognosis remains poor. Additionally, managements for these patients are difficult. Profound postcardiotomy right heart failure developed in a 45-year-old woman after aortic root replacement for critical aortic stenosis with small aortic root. Although maximum medical therapy, intraaortic balloon counterpulsation and extracorporeal membrane oxygenator were attempted, severe right heart failure remained. Finally, an implantable right ventricular assist device (RVAD) was utilized because an immediate myocardial recovery was unlikely. The patient was discharged from the hospital at 17 days after the RVAD implantation. After 79 days of support, right ventricular function had recovered, the fully rehabilitated patient was successfully weaned from the RVAD, and the RVAD was explanted. The patient has no recurrence of heart failure 668 days after RVAD explantation.     

Mechanical cardiac assistance: historical perspectives

Cardiac transplantation remains the therapeutic option of choice for treating patients with chronic, progressive, end-stage heart failure. However, over the past 40 years, a number of mechanical assist systems have been developed with the goal of treating and rehabilitating patients with severe circulatory compromise. Today, a wide array of devices is available to provide increasing levels of circulatory support. When used as bridges to heart transplantation, long-term circulatory support systems are a reliable means of keeping heart-failure patients alive as they await suitable donor hearts. Initially, transplant candidates who were receiving this type of support were unable to leave the hospital; today, however, because of advances in mechanical support technology and the portability of the current systems, these patients may return to their homes and even to their jobs while awaiting transplantation. Although heart transplantation may now be considered a routine procedure, the demand for donor hearts will always outweigh the supply, creating a definite need for long-term mechanical circulatory support. Already, clinical trials are underway to test the effectiveness of left ventricular assist devices as long-term support. As smaller, more effective cardiac assist devices become available, they should benefit even more the number of patients who may need permanent circulatory support. The fact that myocardial function can improve enough with chronic ventricular unloading to allow removal of the device may further broaden the use of this technology.     

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.