Safety and Efficacy of Immunoadsorption as an Add-On to Medical Treatment in Patients with Severe Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Despite optimized medical therapy, severe idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease with a poor outcome. Autoantibodies have been detected in IPAH that can contribute to worsening of the disease. OBJECTIVES: The objective of this prospective, open-label, single-arm, multicenter trial was to evaluate the safety and efficacy of immunoadsorption (IA) as an add-on to optimized medical treatment for patients with IPAH. METHODS: A total of 10 IPAH patients received IA over 5 days. Their clinical parameters, including hemodynamics measured by right heart catheter, were assessed at baseline and after 3 and 6 months. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included the change in 6-min walking distance, quality of life, safety, and plasma levels of IgG and autoantibodies. RESULTS: The evaluation of the 10 IPAH patients (75% female; 51 ± 12 years; 166 ± 10 cm; WHO functional class III; 53% on combination therapy) revealed that IA was a safe procedure that efficiently removed IgG and autoantibodies from the circulation. After 3 months, the mean PVR improved significantly by 13.2% (p = 0.03) and the cardiac index improved by 13.1%, but no significant changes were found in 6-min walking distance. The quality of life physical functioning subscale score significantly improved after 6 months. The serious adverse events in 3 patients were possibly related to IA and included pneumonia, temporary disturbance in attention, and thrombocytopenia. CONCLUSIONS: IA as an add-on to targeted medical treatment for IPAH is a safe procedure with beneficial effects on hemodynamics, especially in patients with high levels of autoantibodies. Larger-scale controlled studies are needed to assess its efficacy in IPAH and to identify responders.

Assessing Anticoagulation Practice Patterns in Patients on Durable Mechanical Circulatory Support Devices: An International Survey.

Anticoagulation in mechanical circulatory support (MCS) patients dictated by local practice, and therefore uniform standards for management are lacking. To characterize the worldwide variance in anticoagulation and antiplatelet therapy in patients with MCS devices, a 42 item survey was created and distributed electronically in August 2014. The survey assessed the center-perceived thromboembolic risk (minimal, low, moderate, or high) and characterized the antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII) and HeartWare HVAD (HVAD). A total of 83/214 centers (39%) responded: North America (60/152), Europe (18/50), Australia (2/4), and Asia (3/8). Although the most common target international normalized ratio (INR) was 2-3 for both devices, significant variability exists. Anticoagulation intensity tended to be lower with the HMII, with more centers targeting INR values of less than 2.5. Aspirin monotherapy was the most common antiplatelet regimen; however, the HVAD patients were more likely to be on daily aspirin doses over 100 mg. In addition, parenteral bridging was more frequent with the HVAD device. While 43.8% of respondents indicated an increase in the perceived risk of HMII device thrombosis in 2014, intensification of anticoagulation (22%) or antiplatelet (11%) therapy was infrequent. Our findings verify the wide variety of anticoagulation practice patterns between MCS centers.

Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta-analysis.

AIMS: Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients. METHODS: We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events. RESULTS: Eight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [-1.17, 12.03] P = 0.32 I(2) = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min(-1) , P = 0.0003] and at 12 months 4.63 [-4.55, 13.82] P = 0.32 I(2) = 75%. CONCLUSIONS: This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.

Prophylactic implantable cardioverter defibrillator treatment in patients with end-stage heart failure awaiting heart transplantation.

OBJECTIVES: This study was designed to delineate the role of implantable cardioverter defibrillator (ICD) therapy for the primary and secondary prevention of sudden cardiac death in patients listed for heart transplantation. SETTING: Retrospective observational multicentre study. PATIENTS: 1089 consecutive patients listed for heart transplantation in two tertiary heart transplant centres were enrolled. Of 550 patients (51%) on the transplant list with an ICD, 216 had received their ICD for the primary prevention of sudden cardiac death and 334 for secondary prevention. 539 patients did not receive an ICD. INTERVENTION: Treatment with or without an ICD was left to the discretion of the heart failure specialist. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: ICDs appear to be associated with a reduction in all-cause mortality in patients implanted with the device for primary and secondary prevention compared to those without an ICD despite a median time on the waiting list of only 8 months (estimated 1-year: 88±3% vs. 77±3% vs. 67±3%; p=0.0001). A Cox regressional hazard model (corrected for age, sex, underlying heart disease, atrial fibrillation, cardiac resynchronisation therapy, New York Heart Association (NYHA) class, ejection fraction, co-medication and year of listing) suggested an independent beneficial effect of ICDs that was most pronounced in patients who had received an ICD for primary prevention (HR 0.4, 95% CI 0.19 to 0.85; p=0.016). CONCLUSIONS: ICD implantation appears to be associated with an immediate and sustained survival benefit for patients awaiting heart transplantation.

Everolimus immunosuppression in de novo heart transplant recipients: what does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.

Lower body surface area is highly related to mortality due to stroke or systemic bleeding in patients receiving an axial flow blood pump as a left ventricular assist device.

OBJECTIVES: Even though left ventricular assist devices (LVADs) may fit into the bodies of small adult patients, their prognosis is worse than that of larger patients. We investigated the relationship between lethal complications and the body surface area (BSA) in patients who received an LVAD. METHODS: Our study included 167 patients who received a BerlinHeart INCOR LVAD in our centre. The median BSA was 2.00 m(2) (range: 1.56-2.47 m²). From the line graph showing the relationship between the BSA for the cut-off point and the P-value of the log-rank test for the Kaplan-Meier probability of freedom from events, the definitive cut-off point was determined on the basis that, with a decrease in the BSA below this value, the P-value gradually increases. RESULTS: For freedom from death due to stroke or systemic bleeding, a definitive cut-off point existed and this was a BSA of 1.867 m(2). For freedom from death due to sepsis, no definitive cut-off point was found. The multivariate Cox analysis revealed that a BSA of <1.867 m(2) was an independent risk factor for death due to stroke or systemic bleeding (hazard ratio: 2.665, 95% confidence interval: 1.349-5.265, P = 0.0048). One-year freedom from death due to stroke or systemic bleeding during the VAD support was 49.1% in patients with a BSA of <1.867 m(2) (n = 42) and 82.7% in those with a BSA of ≥ 1.867 m(2) (n = 125; P = 0.0033). CONCLUSIONS: The lower BSA is an independent risk factor for mortality due to stroke or systemic bleeding during the VAD support.

Everolimus in heart transplantation: an update.

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

Pre-explant stability of unloading-promoted cardiac improvement predicts outcome after weaning from ventricular assist devices.

BACKGROUND: Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF >45 before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation. METHODS AND RESULTS: Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial "off-pump" trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWT(ED)) and end-diastolic short/long-axis ratio (S/L(ED)) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences (P<0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 94 and 100, 92, and 100, and 78 and 100, respectively. Using for all parameter changes the cutoff value of 10, we found similar predictive values for cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively. CONCLUSIONS: Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials.

Arterial wall histology in chronic pulsatile-flow and continuous-flow device circulatory support.

BACKGROUND: Continuous-flow (CF) ventricular assist devices (VAD) are an established option for treatment of end-stage heart failure. However, the effect of long-term CF with lack of peripheral arterial wall motions on blood pressure regulation and end-organ arterial wall sclerosis, especially in the case of long-term support (> 3 years), remains unclear. METHODS: Tissue samples obtained at autopsy from liver, kidney, coronary arteries, and brain from 27 VAD recipients supported for > 180 days between 2000 and 2010 were histologically examined to assess vascular alterations, including perivascular infiltrate, intravascular infiltrate, wall thickness, thrombosis, endothelial cell swelling, vessel wall necrosis, and peri-vascular fibrosis. Pulsatile-flow (PF) devices had been inserted in 9 patients and CF devices had been inserted in 16. The pathologist was blinded to the group distribution. Demographic, pharmacologic, and clinical data were retrospectively analyzed before surgery and during the follow-up period of up to 24 months. RESULTS: Median duration of support was 467 days (range, 235-1,588 days) in the PF group and 263 days (range, 182-942 days) in the CF group. Demographic and clinical data before and after surgery were similar. Amiodarone was more often used during follow-up in CF group than in the PF group (61% vs 10%, p = 0.009). Throughout the follow-up period, mean arterial pressure did not differ between recipients of the 2 pump types, nor did systolic and diastolic pressure, except at 2 weeks after VAD implantation, when systolic blood pressure was higher (p = 0.05) and diastolic lower (p = 0.03) in the PF group. Histologic studies did not identify any relevant differences in arterial wall characteristics between the 2 groups. CONCLUSION: Long-term mechanical circulatory support with CF devices does not adversely influence arterial wall properties of the end-organ vasculature.

Long-term benefits of immunoadsorption in ß(1)-adrenoceptor autoantibody-positive transplant candidates with dilated cardiomyopathy.

AIMS: Prolongation of waiting times for heart transplantation (HTx) increases the need for new therapies. In short-term follow-up studies, immunoadsorption (IA) appeared beneficial in dilated cardiomyopathy (DCM) associated with ß(1)-adrenoreceptor-autoantibodies (ß(1)-AABs). This study aimed to investigate the long-term benefits of IA in HTx candidates with DCM, patients' responsiveness to IA, and the impact of ß(1)-AAB removal on IA results. METHODS AND RESULTS: In a single-centre retrospective study of prospectively gathered information we evaluated all ß(1)-AAB-positive and -negative HTx candidates with end-stage DCM [left ventricular ejection fraction (LVEF) <30%] who underwent IA between 1995 and 2005 (follow-up thereafter: 5.3-14.7 years). As controls we used all ß(1)-AAB-positive DCM patients referred for HTx during the same time period who received no IA therapy. We also looked for differences in efficacy between unspecific IA (unselective antibody removal) and specific IA (selective ß(1)-AAB removal). The main outcome measures were cardiac function and HTx/ventricular assist device (VAD)-free patient survival. The probability for 5-year HTx/VAD-free survival for the108 ß(1)-AAB-positive DCM patients who underwent unspecific IA reached 69.4 ± 4.4% and was significantly higher (P < 0.05) than for both ß(1)-AAB-positive DCM patients without IA (25.4 ± 11.4%) and ß(1)-AAB-negative DCM patients who also underwent IA (47.4 ± 11.5). In patients with high ß(1)-AAB levels, unspecific and specific IA showed the same high efficiency in ß(1)-AAB removal. LVEF and New York Heart Assocation class improved (P < 0.01) after both, but without differences in improvement after specific or unspecific IA. The prevalence of responders to specific and unspecific IA was similar (78.3% vs. 79.6%). In 76% of the patients with ß(1)-AAB reappearance, redetection of AABs coincided with worsening of cardiac function. CONCLUSIONS: Removal of ß(1)-AABs by specific or unspecific IA can improve cardiac function allowing long-term stability in end-stage DCM, which can spare many patients from HTx or will delay HTx listing for years. In ß(1)-AAB-positive DCM patients the benefits of IA appeared to be associated with the removal of these antibodies.

Overweight is advantageous for heart-transplant candidates to survive the period of critically ill status.

Although extreme obesity and being underweight are both known as risk factors for mortality in patients with ventricular assist devices (VAD) and in those listed for urgent heart transplantation (HTx), the risk in patients between these extremes is controversial. We investigate the risk of mortality after their progression to critically ill status (i.e., urgency listing or VAD implantation) in patients stratified by body mass index (BMI). Risk of mortality on the waiting list was studied in group N (n = 134), normal weight, BMI: 18.5-24.9 kg/m(2); group OWt (n = 112), overweight, BMI: 25.0-29.9 kg/m(2); and group OB-I (n = 39), obesity class I, BMI: 30.0-34.9 kg/m(2). Patients' 1 year survival rate on the waiting list in group N (62.2%) and group OB-I (50.6%) was significantly lower than in group OWt (74.3%, p = 0.036 and p = 0.022, respectively). After adjustment for age, gender, serum creatinine, and primary use of VAD, group OB-I (hazard ratio [HR] 1.971, 95% confidence interval [CI] 1.062-3.659, p = 0.032) and group N (HR 1.792, 95% CI 1.058-3.036, p = 0.030) were at higher risk of mortality compared with group OWt. Overweight HTx candidates have the best prognosis on the waiting list. Obesity class I patients are encouraged to reduce their body weight to at least overweight.

A giant neuroendocrine tumor of the thymus gland causing superior vena cava syndrome.

We describe the case of a 37-year-old man with a rare giant thymic neuroendocrine tumor. The patient presented with a swelling of the neck associated with superior vena cava syndrome and underwent stent implantation in the right innominate vein (brachiocephalic vein). Computed tomography imaging revealed a large tumor of the mediastinum, measuring 15 × 10 × 12 cm. CT-guided core-needle biopsy for histology revealed a thymic carcinoid. Surgical resection of the tumor and repair with interposition of a 14-mm Gore-Tex prosthesis between the left innominate vein and the right atrial appendage were performed. Histopathological analysis classified the tumor as an atypical thymic carcinoid. Postoperative course was uneventful. Since complete resection could not be achieved, the patient received two cycles of peptide-receptor radionuclide therapy followed by conventional radiotherapy, and remains symptom-free at 12 months after surgery.

Cardiac surgery for carcinoid heart disease in 12 cases.

PURPOSE: Cardiac involvement is now a major source of morbidity and mortality in patients with carcinoid tumors. We reviewed patients with carcinoid heart disease who underwent valvular surgery in our center. METHODS: Twelve patients with carcinoid heart diseases underwent cardiac surgery between 2000 and 2008. Patients were divided into two groups: group A (n = 6) comprised patients who survived more than 6 months after cardiac surgery, and group D (n = 6) comprised those who died within 6 months. Preoperative factors were compared between the groups. RESULTS: All the 12 patients with carcinoid heart disease underwent tricuspid valve surgery (3 had tricuspid repair and 9 had tricuspid replacement with a bioprosthetic valve). Postoperative 30-day mortality was 16.7% and 2-year actuarial survival was 50.0%. Median survival after the first diagnosis of carcinoid disease was 4.4 years that from first diagnosis of carcinoid heart disease was 2.7 years. Preoperative median left ventricular ejection fraction in group D (52.5%) was significantly lower than that in group A (67.2%, P < 0.05). There were no statistically significant differences between the groups in other parameters. CONCLUSION: Postoperative prognosis may be worse when preoperative left ventricular ejection fraction is borderline, even if it is within the normal limits. Cardiac evaluation is needed in all patients with carcinoid disease from the earliest time of medical and oncological therapy to improve patient outcome.

Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial.

OBJECTIVES: We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. BACKGROUND: Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. METHODS: A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. RESULTS: Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p < 0.001), requirement of LVAD (HR: 6.65; 95% CI: 2.40 to 18.45; p < 0.001), and hemofiltration (HR: 2.83; 95% CI: 1.20 to 6.69; p = 0.02) were predictive of death. The survival benefit remained (HR: 0.33; 95% CI: 0.12 to 0.89; p = 0.03) after adjustment for various risks affecting mortality, including pre-transplant LVAD/BVAD, inotropic support, and impaired kidney function. CONCLUSIONS: Treatment of brain-dead donors with dopamine of 4 µg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115).

Everolimus prevents endomyocardial remodeling after heart transplantation.

BACKGROUND: Endomyocardial remodeling is characterized by progressive fibrosis and scars and may develop after heart transplantation. The role of everolimus in preventing this process has not been evaluated as yet. METHODS: We prospectively studied 132 patients at baseline pretransplant and at 4 weeks, 1 year, and 3 years after heart transplantation. Fibrosis, scars (Zeiss Vision, in Sirius), and acute cellular rejection (hematoxylin-eosin) were studied in biopsy. Transplant vasculopathy was assessed by coronary angiography (focal stenoses, peripheral obliterations, negative vascular remodeling defined by peripheral obliterations, and diffusely narrowed proximal and mid vessel segments). RESULTS: Patients on everolimus versus patients on mycophenolate mofetil presented with significantly less fibrosis at 4 weeks (3.8%±0.3% vs. 5.5%±0.3%, P=0.007), 1 year (4.1%±0.3% vs. 4.8%±0.3%, P=0.015), and 3 years (4.2%±0.3% vs. 5.5%±0.7%, P=0.049) posttransplant and showed less scarring at 3 years posttransplant (19.9±1.9% vs. 31.9±4.6% vs. baseline biopsy 26.0±2.8%; P=0.017). Angiographic peripheral obliterations correlated with higher amounts of endomyocardial fibrosis. The negative correlation of everolimus and the positive correlation of peripheral obliterations with fibrosis were confirmed by regression analysis. Angiographic stenoses or acute cellular rejection had no effect on the development of fibrosis. Negative vascular remodeling in 1-year follow-up tended to be less frequent in everolimus-treated patients (24% vs. 76%; P=0.053). CONCLUSIONS: Everolimus prevents endomyocardial remodeling after heart transplantation and might have beneficial effects on vascular remodeling of epicardial coronary arteries too. Angiographic peripheral obliterations correlate with increased amounts of endomyocardial fibrosis, suggesting a relevant effect on microvascular perfusion.

Retrospective hemolysis comparison between patients with centrifugal biventricular assist and left ventricular assist devices.

Little is known about the hemolysis rate in the case of concomitant implantation of two continuous flow pumps for the treatment of biventricular heart failure. We present a retrospective study comparing the hemolysis parameters in patients supported with one implantable centrifugal pump of the type HeartWare HVAD used as a left ventricular assist device (LVAD) and with two pumps as a biventricular assist device (BiVAD). A total of 20 consecutive patients who received HeartWare BiVAD (n = 10) and LVAD (n = 10) support at our institution between September 2009 and September 2010 were examined. Hemolysis- and anemia-related parameters were analyzed after 2 weeks, 5 weeks, 3 months, and 6 months of support. Preoperative levels of hemoglobin, lactate dehydrogenase (LDH), and total bilirubin were similar in both groups. There were no differences in LDH, plasma-free hemoglobin (fHB), or total bilirubin levels postoperatively for up to 6 months. Only the haptoglobin level was lower in BiVAD recipients up to 3 months after surgery: 2nd week (63.5 [range: 8-237] mg/dl vs. 151 [range: 11-263] mg/dl, p = 0.05), 5th week (67 [range: 8-196] mg/dl vs. 215 [range: 56-292] mg/dl, p = 0.046), and after 3rd month (42 [range: 8-205] mg/dl vs. 220 [range: 157-256] mg/dl, p = 0.048). Our retrospective analysis of BiVAD HeartWare and LVAD HeartWare recipients showed a lack of a clinically important degree of hemolysis when two centrifugal HeartWare pumps are used for biventricular support.

Mechanical circulatory support-results, developments and trends.

The implantation of ventricular assist devices (VADs) is a valuable option in patients with end-stage heart failure. The number of VAD implantations is growing worldwide. Between July 1987 and July 2010, we implanted 1,598 VADs in 1,455 patients. The majority were male (81.0%), and their mean age was 49.4 years (range 0.3-82 years). Indications for implantation were: cardiomyopathy (n = 1,074), post-cardiotomy heart failure (n = 282), acute myocardial infarction (n = 83), graft failure after heart transplantation (n = 64), and others (n = 61). In 55.5%, the VAD implanted was left ventricular, in 39.5% biventricular, and in 4.8% right ventricular. Until 1995, the implanted pumps were mostly pulsatile. Today, however, more than 95% of the implanted VADs are continuous-flow rotary pumps. The average support time was 148.6 days (range 0-1,836 days). The percentage of biventricular VADs has dropped over the years to 20% in 2009. Three hundred forty-seven patients could be successfully bridged to heart transplantation. In 122 patients (8.3%), the device could be explanted after myocardial recovery. In 2009, 31.4% of the patients were implanted for permanent support. During the study period, 521 patients could be discharged home or to a rehabilitation center. Implantation of ventricular assist devices is now an established treatment for patients with both acute and chronic end-stage heart failure. Small implantable left ventricular assist devices of the second and third generation are now broadly employed worldwide, with growing acceptance and decreasing complications. The percentage of biventricular support has dropped over the years to 20%.

Neurohumoral and inflammatory markers for prediction of right ventricular failure after implantation of a left ventricular assist device.

PURPOSE: Implantation of a left ventricular assist device (LVAD) is an established treatment for end-stage heart failure. Right ventricular dysfunction develops in 20%-50% of patients after device implantation, leading to prolonged hospital stays and elevated mortality rates. However, prediction of right ventricular failure remains difficult. METHODS: A total of 40 patients who received an LVAD for chronic end-stage heart failure between May 2001 and December 2002 were evaluated. The patients were divided retrospectively into two groups: group I (n = 26), with no apparent postoperative right ventricular failure; and group II (n = 14), with right ventricular failure after implantation defined by the presence of two of the following criteria during the first week after surgery: mean arterial pressure ≤ 55 mmHg, central venous pressure ≥ 16 mmHg, mixed venous saturation ≤ 55%, cardiac index <2 l/min/m(2), inotropic support score >20 units or an apparent need for mechanical right ventricular support. Hemodynamic, echocardiographic, neurohumoral, and inflammatory parameters were evaluated 24 h before implantation of the LVAD. RESULTS: Levels of procalcitonin, neopterin, n-terminalpro-brain natriuretic peptide, and big endothelin-1 were significantly lower in group I: 0.106 vs. 0.322 ng/ml, P = 0.048; 10.5 vs. 20.7 ng/ml, P = 0.018; 6322 vs. 17174 pg/ml, P = 0.032; 1.6 vs. 19.5 pg/ml, P = 0.02, respectively. Levels of creatinine kinase and creatinine were significantly lower in group I than in group II: 24 vs. 40 U/l, P = 0.034; 1.3 vs. 2.3 mg/dl, P = 0.008, respectively. CONCLUSION: Preoperative evaluation of markers of inflammation and neurohumoral activation may provide additional information for predicting right ventricular failure after implantation of an LVAD.

Heart failure reversal by ventricular unloading in patients with chronic cardiomyopathy: criteria for weaning from ventricular assist devices.

AIMS: Unloading-promoted reversal of heart failure (HF) allows long-term transplant-free outcome after ventricular assist device (VAD) removal. However, because few patients with chronic cardiomyopathy (CCM) were weaned from VADs (the majority only recently), the reliability of criteria used for weaning decisions to predict long-term post-weaning success is barely known. After 15 years of weaning experience, we assessed this issue. METHODS AND RESULTS: In 47 patients with CCM as the underlying cause for HF, who were part of a total of 90 patients weaned from bridge-to-transplant-designed VADs since 1995, we analysed data on cardiac morphology and function collected before VAD implantation, echocardiographic parameters recorded during 'off-pump' trials, duration of HF before implantation, and stability of recovery before and early after VAD removal. Post-weaning 5 year freedom from HF recurrence reached 66%. Only five patients (10.6%) died due to HF recurrence or weaning-related complications. Pre-explantation off-pump left ventricular ejection fraction (LVEF) of ≥50 and ≥45% revealed predictive values for cardiac stability lasting ≥5 years after VAD removal of 91.7 and 79.1%, respectively. With each unit of LVEF reduction, the risk of HF recurrence became 1.5 times higher. The predictive value of LVEF ≥45% also became >90% if additional parameters like pre-explantation LV size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and HF duration before VAD implantation were also considered. Definite cut-off values for certain parameters (including tissue-Doppler-derived LV wall motion velocity) allowed formulation of weaning criteria with high predictability for post-weaning stability, also in patients with incomplete cardiac recovery. CONCLUSIONS: Ventricular assist device removal in CCM patients is feasible and can be successful even after incomplete cardiac recovery. Parameters of pre-explantation cardiac function, LV size and geometry, their stability during final off-pump trials, and HF duration allow detection of patients with the potential to remain stable for >5 post-weaning years.

Adult candidates for heart transplantation with larger body surface area have better prognosis on waiting list after progression to critically ill status.

OBJECTIVE: Smaller body size is one of the characteristics of female patients. We analyzed whether lower body surface area (BSA) of adult patients affects their prognosis after listing for heart transplantation (HTx). METHODS: Adult candidates (≥ 18 and <65 years) for de novo HTx in our center, who were newly listed as T (transplantable) by Eurotransplant without ventricular assist device (VAD) support between 2000 and 2009 (n = 545), were studied. The patients were divided into two groups: group S (n = 272): BSA<1.9563 m(2) (median value of total patients) and group L (n = 273): BSA ≥ 1.9563 m(2). Most female patients (82/84, 97.6%) belong to group S. Among all these patients, 286 progressed to critically ill status, that is, they were listed in urgent status or received a VAD. Actuarial survival rates were studied in each group. RESULTS: Overall survival rates after listing for HTx in group S were comparable to those in group L (43.0% vs 43.7% for 7-year survival, p=0.95). However, 1-year survival rate on waiting list after progression to critically ill status in group S (58.0%, n = 135) and that of female patients in group S (55.8%, n = 33) were significantly lower than those in group L (67.3%, n = 151, all were men; p = 0.042 and p = 0.044, respectively). After multivariate Cox analysis, BSA<1.9563 m(2) (hazard ratio 2.120, p = 0.0019), serum creatinine (hazard ratio 1.202, p = 0.033), obesity defined as body mass index ≥ 30 kg m(-2) (hazard ratio 2.043, p = 0.0096) and primary use of VAD (hazard ratio 3.243, p < 0.0001) were identified as independent risk factors for mortality on waiting list after progression to critically ill status. One-year survival rate on waiting list after VAD implantation in group S (44.4%, n = 65) and that of female patients in group S (38.1%, n = 14) were significantly lower than those in group L (63.0%, n = 78, all were men; p = 0.020 and p = 0.012, respectively). CONCLUSIONS: Adult HTx candidates with lower BSA, including most women, had worse prognosis on waiting list after progression to critically ill status, especially after VAD implantation. As almost all HTx are nowadays performed in critical status, this problem has emerged as important.