State of the art: implantable ventricular assist devices.

PURPOSE OF REVIEW: The first generation of implantable pulsatile ventricular assist devices (VADs) has proven to be successful as bridge to transplantation. Adverse events such as mechanical failure and infections, however, limit their use for long-term support (>1 year) or as alternative for heart transplantation. Newer second generation of nonpulsatile VADs shows less of such limitations. RECENT FINDINGS: As bridge to transplantation, we have seen a switch from pulsatile volume-displacement devices, like the HeartMate XVE LVAS and Novacor left ventricular assist device (LVAD), (first generation) to continuous flow devices like the HeartMate 2 and Berlin Heart Incor (second generation). These devices are smaller, quiet and mechanically more durable. Better long-term survival, lower infection rates, excellent mechanical durability and acceptable quality of life together with shortage of donor organs led also to an increasing usage of these devices as alternative to transplantation. Recent studies show in this respect encouraging results, with actuarial survival rates at 1 and 2 years of 70% or higher. Another result of long-term cardiac support is a bridge to recovery. Initial results of even smaller implantable centrifugal pumps like the HeartWare VAD are promising. SUMMARY: An overview of recent developments in mechanical circulatory support is presented.

Left ventricular assist device: a functional comparison with heart transplantation.

BACKGROUND: A growing number of patients with end-stage heart failure undergo implantation of ventricular assist devices as a bridge to heart transplantation. OBJECTIVES: In this study we investigated whether functional and haemodynamic recovery after implantation is sufficient to warrant the use of them as long-term alternative to heart transplantation. METHODS: We compared peak VO(2) of a group of patients three months after implantation of a ventricular assist device and three months after heart transplantation. Furthermore, we analysed the degree of haemodynamic recovery, by comparing plasma levels of BNP and creatinine before and after implantation of the device. RESULTS: After implantation of a ventricular assist device, exercise capacity improved considerably; three months after implantation peak VO(2) was 20.0+/-4.9 ml/kg/min (52% of predicted for age and gender). After heart transplantation exercise capacity improved even further; 24.0+/-3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the three months after implantation, BNP plasma levels decreased from 570+/-307 pmol/l to 31+/-25 pmol/l and creatinine levels decreased from 191+/-82 mumol/l to 82+/-25 mumol/l, indicating significant unloading of the ventricles and haemodynamic recovery. CONCLUSION: With regard to functional and haemodynamic recovery, the effect of implantation of a ventricular assist device is sufficient to justify its use as an alternative to heart transplantation. (Neth Heart J 2008;16:41-6.).

Guidelines for heart transplantation.

Based on the changes in the field of heart transplantation and the treatment and prognosis of patients with heart failure, these updated guidelines were composed by a committee under the supervision of both the Netherlands Society of Cardiology and the Netherlands Association for Cardiothoracic surgery (NVVC and NVT).THE INDICATION FOR HEART TRANSPLANTATION IS DEFINED AS: 'End-stage heart disease not remediable by more conservative measures'.CONTRAINDICATIONS ARE: irreversible pulmonary hypertension/elevated pulmonary vascular resistance; active systemic infection; active malignancy or history of malignancy with probability of recurrence; inability to comply with complex medical regimen; severe peripheral or cerebrovascular disease and irreversible dysfunction of another organ, including diseases that may limit prognosis after heart transplantation.Considering the difficulties in defining end-stage heart failure, estimating prognosis in the individual patient and the continuing evolution of available therapies, the present criteria are broadly defined. The final acceptance is done by the transplant team which has extensive knowledge of the treatment of patients with advanced heart failure on the one hand and thorough experience with heart transplantation and mechanical circulatory support on the other hand. (Neth Heart J 2008;16:79-87.).

End-stage heart failure and mechanical circulatory support: feasibility of discharge from hospital.

BACKGROUND.: Due to the shortage of donor hearts, mechanical circulatory support is increasingly being used as a bridge to transplantation. In order to allow for more widespread use of ventricular assist devices it is mandatory that patients are not continuously hospitalised. We present the results of our experience with patients with end-stage heart failure, discharged from hospital after implantation of a ventricular assist device and followed in an outpatient setting. METHODS.: After an intensive training and education programme, focusing on the management of the percutaneous driveline and instructions on how to handle in case of an alarm or malfunction of the device, patients were discharged. They were followed in the outpatient department. All regular and unplanned visits were registered, including readmissions. RESULTS.: Twenty-seven patients treated with a ventricular assist device were discharged from hospital. There were 37 extra visits, of these, 27 were device related resulting in 21 readmissions (0.78/patient). We treated eight infectious episodes in four patients, all device related. Furthermore seven thromboembolic episodes occurred in four patients. One patient died because of multiorgan failure seven weeks after he was readmitted with an urosepsis. In our experience of 11.4 patient years at home while on the device, only 5% of the time was spent in hospital for complications. In comparison with patients on an assist device who stayed in hospital until transplantation, there were no more complications. CONCLUSION.: This study demonstrates that patients with end-stage heart failure, treated with a ventricular assist device, can be safely discharged from hospital, with an acceptable rate of readmissions. It results in a fair quality of life, with a high degree of independence of the patient. (Neth Heart J 2007;15:45-50.).

Heart transplantation in the Netherlands: quo vadis?

Heart transplantation is limited by the lack of donor organs. Twenty years after the start of the Dutch transplant programmes in Rotterdam and Utrecht the situation has even worsened, despite efforts to increase the donor pool. The Dutch situation seems to be worse than in other surrounding countries, and several factors that may influence donor organ availability and organ utilisation are discussed. The indications and contraindications for heart transplantation are presented, which are rather restrictive in order to select optimal recipients for the scarce donor hearts. Detailed data on donor hearts, rejected for transplantation, are shown to give some insight into the difficult process of dealing with marginal donor organs. It is concluded that with the current low numbers of acceptable quality donor hearts, there is no lack of capacity in the two transplanting centres nor is the waiting list limiting the number of transplants. The influence of our current legal system on organ donation, which requires (prior) permission from donor and relatives, is probably limited. The most important determinants of donor organ availability are: 1. The potential donor pool, consisting of brain dead victims of (traffic) accidents and CVAs and 2. Lack of consent to a request for donation. The potential donor pool is remarkably small in the Netherlands, due to relatively low numbers of (traffic) accidents, with an almost equal number of CVA-related brain dead patients compared with neighbouring countries. Lack of consent can only be pushed back by improved public awareness of the importance of donation and improved skills of professionals in asking permission in case there is no previous consent.

Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction.

OBJECTIVES: We sought to investigate the origin of the fractionated electrogram and its relations to abnormal conduction in cardiomyopathic myocardium. BACKGROUND: Patients with dilated cardiomyopathy have a high incidence of ventricular tachycardias. Electrograms recorded in these patients are often fractionated. METHODS: High resolution mapping (200-microM interelectrode distance) of the electrical activity was carried out in 11 superfused papillary muscles and 6 trabeculae from 7 patients who underwent heart transplantation because of dilated cardiomyopathy. Similar measurements were taken in four papillary muscles from dog hearts in which electrical barriers had been artificially made. Ten human preparations were studied histologically. RESULTS: All preparations revealed sites with fractionated electrograms. In three human preparations, activation patterns showed a discernible line of activation block running parallel to the fiber direction. Fractionated electrograms were recorded at sites contiguous to the line of block. In five preparations, fractionated electrograms were recorded at sites where lines of block were not identified. In these preparations, electrical barriers consisted of short stretches of fibrous tissue. In the remaining nine preparations, fractionated electrograms were recorded, both from sites contiguous to distinct obstacles and sites without evidence of a barrier. CONCLUSIONS: Our observations showed that fractionated electrograms recorded in myocardium damaged by cardiomyopathy were due to both distinct, long strands and short stretches of fibrous tissue. Delayed conduction was caused by curvation of activation around the distinct lines of block and by the wavy course of activation between the short barriers. The latter reflects extreme nonuniform anisotropy.

Exercise performance in patients with end-stage heart failure after implantation of a left ventricular assist device and after heart transplantation: an outlook for permanent assisting?

OBJECTIVES: We sought to study exercise capacity at different points in time after left ventricular assist device (LVAD) implantation and subsequent heart transplantation (HTx). BACKGROUND: The lack of donor organs warrants alternatives for transplantation. METHODS: Repeat treadmill testing with respiratory gas analysis was performed in 15 men with a LVAD. Four groups of data are presented. In group A (n = 10), the exercise capacities at 8 weeks and 12 weeks after LVAD implantation were compared. In group B (n = 15), the data at 12 weeks are presented in more detail. In group C (n = 9), sequential analysis of exercise capacity was performed at 12 weeks after LVAD implantation and at 12 weeks and one year after HTx. In group D, exercise performance one year after HTx in patients with (n = 10) and without (n = 20) a previous assist device was compared. RESULTS: In group A, peak oxygen consumption (Vo2) increased from 21.3+/-3.8 to 24.2+/-4.8 ml/kg body weight per min (p < 0.003), accompanied by a decrease in peak minute ventilation/ carbon dioxide production (VE/Vco2) (39.4+/-10.1 to 36.3+/-8.2; p < 0.03). In group B, peak Vo2 12 weeks after LVAD implantation was 23.0+/-4.4 ml/kg per min. In group C, levels of peak Vo2 12 weeks after LVAD implantation and 12 weeks and one year after HTx were comparable (22.8+/-5.3, 24.6+/-3.3 and 26.2+/-3.8 ml/kg per min, respectively; p = NS). In group D, there appeared to be no difference in percent predicted peak Vo2 in patients with or without a previous LVAD (68+/-13% vs. 74+/-15%; p < 0.37), although, because of the small numbers, the power of this comparison is limited (0.45 to detect a difference of 10%). CONCLUSIONS: Exercise capacity in patients with a LVAD increases over time; 12 weeks after LVAD implantation, Vo2 is comparable to that at 12 weeks and one year after HTx. Previous LVAD implantation does not seem to adversely affect exercise capacity after HTx.

Reduction of reperfusion injury of human myocardium by allopurinol: a clinical study.

To determine the possibility of myocardial protection against reperfusion injury by allopurinol, 22 aortocoronary bypass patients were studied. Eight patients received allopurinol (200 mg during induction of anesthesia and 100 mg after starting extracorporeal circulation) during surgery (group B), and 14 patients served as a control (group A). Blood samples and myocardial biopsies were taken before and 10 min after aortic cross-clamping. No statistically significant difference between the two groups was observed considering gender, age, prior myocardial infarction, left ventricular end diastolic pressure (LVEDP), and aortic cross-clamp time. Preservation of cardiac tissue was assessed by the measurement of quantitative birefringence (QBR) changes upon the addition of adenosine 5'-triphosphate (ATP) plus calcium in biopsies and the need for postoperative inotropes. The synthesis of peroxides was estimated by the measurement of leukotriene B4 and C4 (LTB4, LTC4). LTB4 was below the level of detection (< 1.5 ng/l) before and after cross-clamping in both groups, while the LTC4 level for group A increased from < 1.5 to 27 +/- 17 ng/l compared to an increase of < 1.5 to 11 +/- 8 ng/l for group B after 10 min of reperfusion (p = .036). The decrease in QBR value in group A was 1.26 +/- 0.28 and 0.35 +/- 0.23 for group B (p < .003). Postoperatively, 11 out of 14 patients in group A needed inotropic support (dopamine or dobutamine), whereas two patients out of eight did so in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery bypass grafting without cardiopulmonary bypass using the octopus method: results in the first one hundred patients.

OBJECTIVE: Cardiopulmonary bypass and global cardiac arrest enable safe coronary artery bypass grafting but have adverse effects. In off-pump coronary bypass grafting, invasiveness is reduced, but anastomosis suturing is jeopardized by cardiac motion. Therefore the key to successful off-pump coronary bypass grafting is effective local cardiac wall stabilization. METHODS: We prospectively assessed the safety and efficacy of the Octopus tissue stabilizer (Medtronic, Inc., Minneapolis, Minn.) in the first 100 patients selected for off-pump coronary bypass via full or limited surgical access. To immobilize and expose the coronary artery, two suction paddles (-400 mm Hg), fixed to the operating table-rail by an articulating arm, stabilized the anastomosis site. RESULTS: One hundred forty-one grafts (96% arterial) were used to create 172 anastomoses (17% side-to-side), up to 4 per patient, on average 23 in the full access group (46 patients) and 1.2 in the limited access group (54 patients). Complications included conversion to cardiopulmonary bypass (2%), conversion from limited to full access (3%), myocardial infarction (4%), predischarge coronary reintervention (2%), and late coronary reintervention (1%). Median postoperative length of hospital stay was 4 days (limited access) or 5 days (full access). Rapid recovery allowed 96% of patients to resume social activities within 1 month. At the 6-month angiographic follow-up, 95% of anastomoses was patent. At the 2- to 22-month follow-up (mean, 13 months), 98 patients were in Canadian Cardiovascular Society class I and 2 patients were in class II. CONCLUSION: These results suggest that off-pump coronary artery bypass grafting with the Octopus tissue stabilizer is safe. Early clinical outcome and patency rates warrant a randomized study comparing this methods with conventional coronary bypass grafting.

Ventricular fibrillation during acute rejection after heart transplantation.

The case of a 46-year-old patient who underwent orthotopic heart transplantation for treatment of end-stage heart failure as a result of ischemic heart disease is reported. Four months after transplantation a grade II rejection episode was complicated by ventricular fibrillation. Lidocaine and procainamide intravenously did not effectively prevent recurrence. An increase of antirejection therapy in combination with flecainide acetate effectively prevented further episodes of ventricular fibrillation. This case demonstrates that recurrent ventricular fibrillation can be a complication of acute rejection.

Comparison of functional capacity in patients with end-stage heart failure following implantation of a left ventricular assist device versus heart transplantation: results of the experience with left ventricular assist device with exercise trial.

BACKGROUND: Use of a permanent left ventricular assist device (LVAD) has been proposed as an alternate treatment of patients with end-stage heart failure. The purpose of this study was to compare the functional capacity of patients following implantation of a LVAD vs heart transplant (HTx). METHODS: Eighteen patients from 6 centers who received an intracorporeal LVAD as a bridge to HTx underwent treadmill testing 1 to 3 months post-LVAD and again post-HTx. Baseline and peak measurements, including oxygen consumption, blood pressures, and respiratory rate were made during each treadmill test. RESULTS: Peak oxygen consumption was 14.5+/-3.9 ml/kg/minute post-LVAD and 17.5+/-5.0 ml/kg/minute post-HTx (p < .005). The percentage of the predicted peak oxygen consumption based on gender, weight, and age was 39.5%+/-5.5% post-LVAD and 47.7%+/-10.9% post-HTx (p < .005). Exercise duration was lower post-LVAD than post-HTx (10.3+/-4.2 minute vs 12.5+/-5.4 minute, p < .05). After LVAD implantation, peak total oxygen consumption correlated with peak LVAD rate and output. Eight patients reached an LVAD rate of 120 beats per minute (bpm) before the conclusion of exercise, the maximum rate for the outpatient electric device. The peak respiratory exchange ratio post-LVAD was 1.15+/-0.22 and post-HTx was 1.15+/-0.18, consistent with a good effort in both groups. CONCLUSIONS: Patients demonstrated a lower functional capacity post-LVAD than post-HTx. For some patients functional capacity post-LVAD may be improved by a higher maximum LVAD rate and output.

Cytokine messenger RNA expression by donor-specific cytotoxic T-cell clones after allogeneic heart transplantation.

BACKGROUND: After heart transplantation, expression of various cytokines can be detected in endomyocardial biopsy specimens both in the presence and in the absence of rejection. In this study we have analyzed the contribution of donor-specific CD8+ cytotoxic T cells to intragraft cytokine expression. METHODS: T cells were propagated from endomyocardial biopsy specimens in medium containing interleukin-2 and interleukin-4. From the T-cell lines obtained, T-cell clones were generated by limiting dilution. A number of 15 CD8+ donor-specific cytotoxic T-cell clones were generated from a single T-cell line and were analyzed for their cytokine messenger RNA expression. The cytokine profile of the clones was studied on the mRNA level by reverse transcriptase polymerase chain reaction. RESULTS: Almost all clones expressed mRNA for interleukin-1 beta, interleukin-4, and interleukin-10, and 75% of the clones expressed mRNA for interleukin-1 alpha, interleukin-9, and tumor necrosis factor-beta. In about half of the clones expression of interleukin-2, interleukin-6, interleukin-8, and interferon-gamma was detected. Tumor necrosis factor-alpha was only detected in one of the clones. The cytokine profiles exhibited a considerable heterogeneity. The 15 clones had previously been analyzed for their T-cell receptor V beta-gene family expression and T-cell receptor V-D-J region sequence. Homology in the V-D-J regions of the clones indicated that the 15 clones were derived from a limited number of progenitor cells. Interestingly, clones derived from one progenitor expressed a different mRNA cytokine profile. CONCLUSIONS: This study shows that donor-specific cytotoxic T cells can contribute to the spectrum of locally produced cytokines. The cytokine expression of these cytotoxic T cells seems not to be limited to a distinct profile.

Off-pump coronary bypass grafting: how to use the Octopus Tissue Stabilizer.

Off-pump coronary artery bypass grafting requires immobilization of the coronary artery. A suction device (Octopus Tissue Stabilizer), attached to the epicardium and connected rigidly to the operating table rail, was used through limited and full surgical access for single-vessel and multivessel arterial revascularization, respectively. An outline for its application, as used by us to construct 122 anastomoses in 70 patients, including posterior wall grafting (in 9 patients) and sequential grafting on the anterior wall (in 17 patients), is presented.

Less invasive off-pump CABG using a suction device for immobilization: the 'Octopus' method.

OBJECTIVE: Target site immobilization is essential to enable meticulous anastomosis suturing during coronary artery bypass grafting on the beating heart. A novel device ('Octopus') was developed for local heart muscle immobilization by suction. The purpose of this study was to investigate the efficacy of the method through a limited access. METHODS: The suction device, placed on either side of the recipient coronary artery and fixed to the operating table-rail through an arm construction, restrains anastomosis site motion to 1 x 1 mm. A total of 27 patients underwent off-pump arterial bypass grafting using this method. Preoperatively, all patients had angina class III (NYHA) and were failed or unsuitable candidates for balloon angioplasty. Surgical access was via a 10-cm anterior thoracotomy (n = 26) or 10-cm subxiphoid incision (n = 1). RESULTS: Harvesting of the graft required 48 +/- 12 min (mean +/- S.D.). Immobilization with the 'Octopus' was effective and facilitated precise anastomosis suturing of 20 single and 7 sequential grafts. Immobilization did not change cardiac index and mean arterial blood pressure. During coronary surgery, however, inotropic drug support was used in 5 of 27 (18%) of patients. There was no myocardial infarction. Only minor transient complications were met. There were electro-cardiographical signs of pericarditis in 6 patients. The postoperative hospital stay ranged from 2 to 6 days, mean 4.0 +/- 1.2 days. The mean follow-up is 6.5 +/- 4 months (range, 1-12 months). All patients except one were in functional class I without angina. Social activities were resumed within 4 weeks. At 6 months angiography was performed in 15 out of 27 patients. The patency rate of 19 out of 20 anastomoses was 95%. All distal grafts were patent. One side to side anastomosis was occluded. CONCLUSIONS: The 'Octopus' immobilization method is safe and effective. It facilitates less invasive CABG in selected patients and gives way to fast recovery by reducing invasiveness.

[Successful pregnancy after heart transplantation]. / Geslaagde zwangerschap na harttransplantatie.

A 32-year-old woman underwent heart transplantation after having suffered two myocardial infarctions, the first when parturition was pharmacologically induced, the second during diagnostic catheterization. Three years after the heart transplantation she became pregnant three times. In the first two pregnancies therapeutic abortion was performed because of trisomy-21. The third pregnancy was uneventful until week 36. At that time labour was induced because of signs of pre-ecclampsia. A healthy boy was born with normal physical and psychological development after four years. In pregnancy after heart transplantation teratogenic effects of the medication have not been described. The main problems are hypertension and pre-eclampsia in the mother and prematurity and low birth weight in the newborn. A major problem is the limited life expectancy after heart transplantation due to which a patient will only rarely see his or her child grow up into adulthood.

Successful aortic valve replacement in a patient with AIDS.

In trying to assess the benefit of cardiac surgery in AIDS patients, the question arises whether a patient with a deficient immune system can tolerate open heart surgery well enough to make the operation worthwhile. Surgical procedures and cardiopulmonary bypass have been noted to alter immune function (Diettrich et al., Ide et al.). Therefore, the presence of clinical AIDS is often still regarded as a contraindication to cardiac surgery. In this report we describe an AIDS patient who developed endocarditis of the native aortic valve. The endocarditis was successfully treated with antibiotic drugs, but the patient was left with damaged valves. Over the months he developed a massive aortic insufficiency and underwent aortic valve replacement. The patient did well after surgery, and is alive and well 18 months after the operation, suggesting that cardiac surgery might be a good and valuable treatment option in AIDS patients.

Left ventricular assist device as bridge to transplantation in patients with end-stage heart failure: Eight-year experience with the implantable HeartMate LVAS.

OBJECTIVE: To evaluate the use of left ventricular assist devices (LVAD) as bridge to heart transplantation (HTx) in patients with end-stage heart failure. METHOD: Between March 1993 and December 2001, 38 patients with refractory end-stage heart failure underwent HeartMate LVAD (Thoratec, Pleasanton Calif.) implantation. RESULTS: A total of 33 of the 38 patients (87%) survived the implantation and perioperative period. There were five perioperative deaths (13%), two due to right ventricular failure, two as a result of bleeding and one probably due to septic shock at the time of LVAD implantation. Three patients (9%) died late in the postoperative period due to septic shock, mechanical failure of the device and a cerebral embolus resulting from LVAD endocarditis, initiated by an acute cholecystitis. Twelve patients (32%) had one or more infectious episodes during long-term assist, of which one patient died. Four patients are still on the device, waiting for a heart transplantation. Twenty-six patients (76%) underwent HTx after 206±129 days of support. CONCLUSION: These results show the efficacy of LVAD support as a bridge to heart transplantation in patients with end-stage heart failure. Major long-term complications are infections and mechanical failure of the device.

Continuous-flow left ventricular assist device support in patients with advanced heart failure: points of interest for the daily management.

Today, continuous-flow left ventricular assist devices (cf-LVADs) are implanted more often in patients with end-stage heart failure. Because of greater durability they can be implanted for an extended period of time. As a result of increased numbers of patients on cf-LVAD support, healthcare professionals should be aware of the potential complications inherent to this therapy. Both bleeding and thrombosis may occur, and also complications related either to the device itself or to the ensuing altered haemodynamics, valvular pathology, and rhythm disturbances such as ventricular tachycardias and fibrillation. Accurate clinical evaluation, together with an electrocardiogram and, if necessary, combined with an echocardiogram, is obligatory in these situations. This review summarizes common complications complemented by a few clinical cases.