J. H. Kirkels

Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias

Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload.

Predictability and other aspects of post-transplant diabetes mellitus in heart transplant recipients.

BACKGROUND Diabetes mellitus that develops after organ transplantation may predispose patients to further complications. We studied the value of pre-transplant oral glucose tolerance testing or maximum random plasma glucose, and HLA-DR3 and/or DR4 phenotype as predictors of post-transplantation diabetes mellitus in heart transplant recipients. PATIENTS AND METHODS In 228 cardiac allograft recipients (median age, 50 years; mean follow-up, 4.77 years), we used either pre-transplant oral glucose tolerance testing results (Group I, n = 141)-excluding patients with pre-existing diabetes (n = 9)--or maximum random plasma glucose values (Group II, n = 78) to study predictability of post-transplant diabetes. In addition, we investigated its relation to rejection treatment and clinical course. RESULTS Cumulative incidence of post-transplant diabetes (n = 43) was 19.6%, 83% of which became manifest within 3 months post-transplant; pre-transplant body mass index was higher (p < 0.01) in this group. Mortality did not increase. Of 123 patients in Group I who survived > 3 months, post-transplant diabetes occurred in 32% vs 16% of those with impaired and normal glucose tolerance respectively (ns), and in 55% of patients with isolated post-load hyperglycemia (p < 0.05 vs normal). Maximum random glucose values (Group II) did not predict post-transplant diabetes. Prevalence of the HLA-DR3, DR4, and DR3DR4 phenotypes did not increase in post-transplant diabetes; relation to rejection treatment was likely in 30%. Approximately 50% of posttransplant diabetes patients required only temporary drug treatment. CONCLUSIONS The risk of post-transplant diabetes increased parallel to pre-transplant degree of glucose intolerance, but was considerable even in normal glucose tolerance. HLA-DR3 and/or DR4 phenotype was not a predisposing factor.

Left ventricular assist device as a bridge to recovery in a young woman admitted with peripartum cardiomyopathy

Left ventricular assist devices (LVAD) are an effective therapeutic option for end-stage heart failure patients as a bridge to cardiac transplantation in those who deteriorate despite maximal therapy and when a donor heart is not ready available. In some patients, cardiac recovery has been reported while supported by an LVAD. In this case report, we describe a 29-year-old female who was admitted to our centre because of peripartum cardiomyopathy (PPCM). Despite intensive treatment with intravenous inotropes and intra-aortic balloon counter-pulsation she had a persisting low cardiac index and an LVAD was implanted. In the months following implantation the left ventricular systolic function improved and the left ventricular dimensions normalised. Eventually the LVAD could be ex-planted nine months after implantation. At this moment, three years after explantation, echo-cardiography shows a normal-sized left ventricle and almost completely recovered systolic function. (Neth Heart J 2008;16:426-8).

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.)

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.

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

AbstractBackground 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 VO2 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 VO2 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 μmol/l to 82±25 μmol/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.)

Assist devices in the new decade: from technical developments to political decisions

Although assist devices have successfully been used for 20 years as a bridge to heart transplantation, there is still an ongoing debate about the use of long-term mechanical circulatory support as an alternative to transplantation. Since the publication of the REMATCH study in 2001, there have been extensive discussions about the optimal treatment of end-stage heart failure. The REMATCH study is still unsurpassed in which patients, non-eligible for heart transplantation, were randomly assigned to optimal medical therapy or mechanical circulatory support with a pusherplate type of left ventricular assist device (LVAD), the HeartMate XVE (Thoratec, Inc., Pleasanton, CA, USA). After 1 year of follow-up, survival in the LVAD group was about twice that in the conservatively treated patients (52 vs. 25%). For the first time, it had been shown that long-term mechanical support was feasible and better than optimal medical treatment. This has led to FDA approval and reimbursement of the HeartMate XVE as a treatment option for end-stage heart failure. Despite high expectations, the number of implants, however, did not grow excessively. Part of this lack of widespread enthusiasm was certainly related to the bulky size of the device, and the very characteristic hissing noise from the device, hampering normal social contacts. Another major problem became evident in the 2-year follow-up, when almost all patients had died in both arms (survival 23% vs. 8%), the major problems in the LVAD group being device failure and device-related infections. None of the study patients lived for more than 3.5 years with their device. These poor long-term results from the REMATCH study shed new light on the cost-effectiveness of LVADs. If the majority of patients were to die within 2 years, LVADs would lack costeffectiveness, often defined as the yearly cost of haemodialysis. In the Netherlands and several other European countries, this has been a major reason for limiting reimbursement of LVADs to patients requiring a bridge to transplant. In 2006, Potapov et al. reported on the use of long-term circulatory support for over 4 years in a small group of non-transplant candidates, proving the feasibility of extended longevity of LVADs in individual patients. Since 2005, the worldwide focus has changed from bulky and noisy pusher-plate pumps to smaller and silent axial flow devices and centrifugal pumps, facilitating more widespread use. Although these continuous-flow pumps soon appeared to surpass the pulsatile-flow devices both in acceptability and longevity, until recently there were only case reports and registries to prove their superiority. In November 2009, the HeartMate DT study was published. This was a randomized study—again in patients unsuitable for heart transplantation—to compare event-free survival between the HeartMate XVE (a pulsatile flow device) and HeartMate II, a continuous flow pump. The primary endpoint was defined as survival free of major neurological complications and pump failure or pump exchange. After a 2-year follow-up, HeartMate II patients did about twice as well as patients on a HeartMate XVE, with an actuarial survival rate of 58 vs. 24%. The difference in the 2-year survival free from disabling stroke and reoperation for device repair or replacement was even more impressive, in favour of the continuous-flow pump compared with the pulsatile-flow device (46 vs. 11%). This difference was mainly driven by a lower rate of pump replacements (9 vs. 34%, respectively). Disabling stroke, both ischaemic and haemorrhagic, remains a real problem with both types of pumps, occurring in about 12% of patients. Quality of life and exercise capacity in uncomplicated LVAD patients are much better than in medically treated patients with end-stage heart failure and comparable with patients after heart transplantation. The lack of need for immunosuppressive therapy may even outweigh the physical limitations of an artificial pump, such as the need to wear batteries and limitations in taking a shower. However, no randomized studies have yet been performed to compare the quality of life of patients with an LVAD and those who have undergone heart transplantation. With respect to ‘longevity’, heart transplantation undoubtedly beats LVADs, with an average survival of about 11 years, although

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.)

Beta-blocker therapy in unstable severe heart failure, evidence or experience?

Currently, no evidence exists on the effects of beta-receptor blocker (BRB) treatment in patients with unstable severe heart failure. When confronted with this specific patient category, clinical experience in our centre has consistently guided us to lower the dose or stop BRB therapy. To share this experience, we present three clinical case scenarios and discuss background literature motivating our approach in these patients.

Non-intubated recovery from refractory cardiogenic shock on percutaneous VA-extracorporeal membrane oxygenation

We report on the use of percutaneous femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in a fully awake, non-intubated and spontaneously breathing patient suffering from acute, severe and refractory cardiogenic shock due to a (sub)acute anterior myocardial infarction. Intensified heart failure therapy was closely monitored with a pulmonary artery catheter and allowed gradual weaning off the ECMO support without additional invasive measures, notably without mechanical ventilation. Neurological assessment was possible at all times and complete physical mobilisation was straightforward directly after weaning from ECMO. This limited invasive approach may encourage a more widespread use of percutaneous VA-ECMO.