International experience using a durable, centrifugal-flow ventricular assist device for biventricular support.

BACKGROUND: Heart transplantation is limited by the scarcity of suitable donors. Patients with advanced biventricular failure may require biventricular support to provide optimal cardiac output and end-organ perfusion. We highlight the outcomes of using the HeartWare HVAD System (HVAD) in a biventricular configuration. METHODS: This retrospective study included patients implanted with HVAD as a biventricular assist device (BiVAD) between 2009 and 2017 at 12 participating centers. When used as a right ventricular assist device (VAD) (RVAD), the HVAD can be attached to the right ventricle (RV) or the right atrium (RA). Kaplan-Meier survival estimates were calculated comparing the 2 RVAD implant locations. Comparisons were also made between the timing of RVAD implantation (primary vs staged) on adverse event (AE) profiles and survival. RESULTS: Among the 93 patients who were implanted with a HVAD BiVAD, Kaplan-Meier survivals at 1-year and 2-year were 56% and 47%, respectively. Survival was independent of the location of the HVAD RVAD implant or whether there was an interval between left VAD and RVAD implantation. The most common AEs were bleeding (35.5%), infection (25.8%), and respiratory failure (20.4%). CONCLUSIONS: This study illustrated similar survival in patients receiving a primary or staged HVAD BiVAD implant at 1 year and 2 years. This study also established that the locations of the RVAD implant (RV or RA) result in similar AE profiles.

Effective treatment with a new protocol using tissue-type plasminogen activator thrombolysis for pump thrombosis with the HVAD device.

BACKGROUND:: Pump thrombosis is a major complication of the continuous flow left ventricular assist device. Pump exchange is seen as the therapeutic gold standard. In this study, we report on our experience with using tissue-type plasminogen activator thrombolysis for therapy of pump thrombosis. METHODS:: We report on our experience with treatment of continuous flow left ventricular assist device pump thrombosis with the HVAD using tissue-type plasminogen activator thrombolysis in nine patients with 16 thrombotic events. In all events we used a uniform treatment protocol. RESULTS:: All patients presented with a sufficient anticoagulation and had symptoms of heart failure. However, all patients were haemodynamically stable. Six of nine patients presented with a mean arterial pressure above 85 mm Hg and every patient presented with an infection. In all events we achieved short-term success with resolution of the pump thrombosis within a median time of nine hours. Three of nine patients developed recurrent pump thrombosis after >60 days. Besides one case of nonfatal intracranial haemorrhage and one case of minor bleeding, there were no adverse events. CONCLUSION:: Our data indicates that using a uniform treatment protocol that builds on usage of tissue-type plasminogen activator thrombolysis might be an effective tool for treatment of continuous flow left ventricular assist device pump thrombosis in haemodynamically stable patients. Additionally, our data indicates that infection may be a potential trigger for pump thrombosis.

Gender differences and outcomes in left ventricular assist device support: The European Registry for Patients with Mechanical Circulatory Support.

BACKGROUND: Despite the increasing use of ventricular assist devices (VADs), gender differences in indications, hemodynamics, and outcome are not well understood. We examined gender differences and gender-specific predictors for perioperative outcome in patients on ventricular support. METHODS: Multicenter data of 966 patients (median age 55 years, 151 women) from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) were analyzed. Median follow-up was 1.26 years. RESULTS: At the time of VAD implantation, women were more often in an unstable condition (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1 and 2) (51.7% vs 41.6% in men), experiencing significantly more often major bleeding (p = 0.0012), arrhythmias (p = 0.022), and right ventricular (RV) failure (p < 0.001) with need for additional RV support. The survival of women on isolated LVAD support was significantly worse (1-year survival 75.5% vs 83.2% in men). Age-adjusted Cox regression analyses showed significant associations with mortality for preoperative inotropic therapy, percutaneous mechanical support, INTERMACS profile 1 and 2, RV dysfunction, major bleeding, cerebral bleeding, ischemic stroke, and RV failure. In women, pump thrombosis was more strongly related with mortality compared to men, while the direction of the association of renal dysfunction with mortality was different for women and men (p-value interaction 0.028 and 0.023, respectively). CONCLUSIONS: Women and men differ in perioperative hemodynamics, adverse events, and mortality after VAD implantation. A gender-dependent association of pump thrombosis with mortality was seen. The impact on treatment practice needs to be shown.

Percutaneous left atrial unloading to prevent pulmonary oedema and to facilitate ventricular recovery under extracorporeal membrane oxygenation therapy.

OBJECTIVES: Left-sided unloading during extracorporeal membrane oxygenation (ECMO) therapy is crucial to prevent pulmonary oedema and facilitate ventricular recovery. We present the case of a 55-year-old man under ECMO therapy with pre-existing left ventricular (LV) thrombus formation and in need of ventricular unloading. METHODS: We implanted a 21-Fr TandemHeart Protek Solo trans-septal cannula into the left atrium using a trans-septal approach via the femoral vein. The cannula was connected to the venous line of the ECMO circuit. A flow probe and a clamp to reduce flow, if necessary, were attached to the left atrium line. Left atrium flow was adjusted to 900 ml/min under transoesophageal echocardiography control to keep the atrial septum in the mid-line and to prevent suction of the inflow cannula. RESULTS: After 9 days, the patient was weaned step-wise from ECMO and the TandemHeart cannula, which was then explanted. The patient is in New York health Association Class II without neurological sequelae (Cerebral Performance Scale 1). After 3 months, the patient has fully recovered and is working daily. The LV function is still moderately impaired, and the size of the LV thrombus remains the same. The atrial septum shows no residual defect. CONCLUSIONS: Percutaneous trans-septal insertion of a TandemHeart cannula incorporated in an ECMO circuit for the prevention of pulmonary oedema and subsequent weaning from extracorporeal circulation was feasible and safe in a patient with cardiogenic shock and an LV thrombus.

The value of fluorine-18 deoxyglucose positron emission tomography scans in patients with ventricular assist device specific infections†.

BACKGROUND: Infections are major complications in patients with ventricular assist devices (VAD). Positron emission tomography with deoxyglucose marked by fluorine-18 ( 18 F-FDG PET/CT) is a diagnostic tool to scan for tissue with high metabolism as present in infections. The specificity of 18 F-FDG PET/CT to discriminate between infection and an aseptic reaction of the implanted device is not defined and its evaluation is the aim of this retrospective analysis. METHODS: Until September 2015 a total of 100 patients underwent VAD implantations in our institution. Twenty-one patients (mean age 53.7 ± 14.3 years) had 29 PET-CT examinations for a suspected infection. All radiology reports were compared to clinical and intraoperative parameters. Infections were reported according to the guidelines of the International Society of Heart and Lung Transplantation. Follow-up was 222 days (range 107-484 days) after PET-CT scans and was complete in all patients. RESULTS: In 7 patients PET-CT scan ruled out any VAD associated infection. Sixteen patients had a VAD specific infection. Two patients had false negative PET-CT scan results. The sensitivity of VAD-specific infections was 87.5%, the specificity 100%, the positive predictive value was 100% and the negative predictive value 86.7%. Seven patients had more than one PET-CT scans at different time points. CONCLUSIONS: PET-CT scan findings showed a high specificity and positive predictive value for VAD-specific infections. Therefore, it may have the potential to guide the clinician in handling patients with infectious complications after VAD implantation.

Outcomes of Minimally Invasive Temporary Right Ventricular Assist Device Support for Acute Right Ventricular Failure During Minimally Invasive Left Ventricular Assist Device Implantation.

Right ventricular failure (RVF) may still occur despite the benefits of minimally invasive left ventricular assist device (MI-LVAD) implantation. Our center strategy aims to avoid aggressive postoperative inotrope use by using mechanical support to facilitate right ventricle recovery and adaptation. We herein report first outcomes of patients with minimally invasive temporary right ventricular assist device (MI-t-RVAD) support for RVF during MI-LVAD implantation. Right ventricular failure was defined as requiring more than moderate inotopic support after weaning from cardiopulmonary bypass according to Interagency Registry for Mechanically Assisted Circulatory Support adverse event definitions. All patients requiring MI-t-RVAD support for RVF during MI-LVAD implantation between January, 2012 and April, 2016 were retrospectively reviewed. Clinical endpoints were death or unsuccessful RVAD weaning. Overall 10 patients (90% male, mean age 49.6 ± 14.8 years) underwent MI-t-RVAD implantation. Duration of MI-t-RVAD support was 16.2 ± 11.6 days. Right ventricular assist device weaning and subsequent uneventful awake device explantation was successful in all cases. The 30 day survival was 80%. Our results confirm safety and feasibility of MI-t-RVAD support for acute RVF in the setting of MI-LVAD implantation. The potential benefits of this strategy are more stable hemodynamics in the first postoperative days that usually are crucial for LVAD patients and reduced inotrope requirement.

Percutaneous Dilatation Tracheostomy in Patients with Left Ventricular Assist Device and Established Phenprocoumon Therapy.

Over the last decade, the number of heart transplantations declined, and the number of implanted left ventricular assist devices (LVADs) markedly increased. Accordingly, common intensive care interventions rise and present their own challenges, especially because of the necessary anticoagulation regimen. One of these procedures is percutaneous dilatation tracheostomy (PDT). We herein report our experience with 34 patients with LVAD and established phenprocoumon therapy (International normalized ratio 2.1 ± 0.9, partial thromboplastin time 68.9 ± 19.0 seconds) who underwent PDT between 2006 and 2015 at our specialized cardiac surgery intensive care unit. Intraprocedural success was achieved in all cases (34/34 patients) with sufficient placement of the tracheal tube and adequate mechanical ventilation. No retained secretions or tracheostomy tube obstructions were observed during follow-up. In no case, conversion to surgical tracheostomy was necessary. No serious bleeding complications that required urgent or emergent reoperation occurred during or after the PDT procedure. A total of 16 patients (47.1%) died within the first 30 days after LVAD implantation. This is the first report describing outcomes of patients with LVAD under established phenprocoumon therapy and postoperative implemented PDT. PDT is a safe procedure for those patients. It is not connected with bleeding complications and shows a good procedural outcome.

Concomitant minimally invasive HVAD and transapical aortic valve implantation.

Minimally invasive left ventricular assist device (LVAD) implantation with the HeartWare VAD (HVAD) has been reported lately as an alternative approach to median sternotomy due to its favorable results regarding sternal wound complications, mediastinitis, postoperative bleeding, and right ventricular failure (RVF). Relevant aortic regurgitation is a cardiac comorbidity that requires surgical repair at the time of LVAD implantation to reduce recirculation and ensure adequate forward flow. We herein report on a patient with severely reduced left ventricular function due to ischemic cardiomyopathy, moderate aortic regurgitation, and a reduced right ventricular function. We performed minimally invasive HVAD implantation with concomitant transapical transcatheter aortic valve replacement. We believe this hybrid procedure could potentially reduce the risk for post-LVAD RVF because it preserves the pericardial geometry and obviates the need for cardioplegic arrest.

Medical and psychosocial predictors of mechanical circulatory support device implantation and competing outcomes in the Waiting for a New Heart Study.

BACKGROUND: Medical and psychosocial factors are related to 1-year outcomes in the Waiting for a New Heart Study. With increased use of mechanical circulatory support devices (MCSD) over the course of the study, we can now evaluate these variables as predictors of MCSD in an extended follow-up. METHODS: Analyses focused on 313 MCSD-free patients (82% men; aged 53 ± 11 years) newly listed for heart transplantation (HTx). Variables assessed at time of listing included psychosocial risk (depression, social isolation), quality of life, waiting list stress, and medical risk (Heart Failure Survival Score, pulmonary capillary wedge pressure). Cumulative incidence functions and cause-specific Cox models examined the association of medical and psychosocial risk (low: non-depressed and socially integrated; medium: depressed or socially isolated; high: depressed and socially isolated) with time until MCSD, considering covariates and competing outcomes (death, high-urgency transplantation [HU-HTx], elective HTx, and delisting due to clinical improvement or deterioration). RESULTS: Psychosocial risk groups were comparable regarding demographics, medical parameters, and quality of life, but differed in waiting list-related stressors. During follow-up (median, 326; range, 5-1,849 days), 26 patients received MCSD, 53 died, 144 underwent HTx (103 in HU status), and 53 were delisted (15 deteriorated, 31 improved). Non-depressed and socially integrated patients did not require MCSD. Controlling for medical risk, psychosocial risk significantly contributed to MCSD, HU-HTx, and improvement; medical risk and female gender predicted death (p < 0.05). CONCLUSIONS: Psychosocial risk at time of listing affects the prognosis of HTx candidates beyond medical risk. Psychosocial interventions may help to stabilize patients' health.

First successful use of the new ab5000 portable circulatory support console as bridge to recovery in a case of dilated cardiomyopathy.

INTRODUCTION: Growing clinical experience and improved technology have led to more widespread use of ventricular assist devices in patients with end-stage heart failure. METHODS: We report the case of a patient with preexisting cardiomyopathy who arrived at our center in cardiogenic shock and received a biventricular assist device. RESULTS: The new compact Abiomed Portable Circulatory Support Console facilitated mobilization of the patient which was particularly advantageous in the face of transient hemiparesis. After recovery from cardiogenic shock, device removal was performed following a bridge-to-recovery concept. He was discharged in a state of full cardiac recompensation and is back to everyday life with stable cardiac function up to 24 months after the incident. CONCLUSIONS: This is the first report describing successful clinical use of the AB5000 assist device in combination with the portable console. Furthermore, it underlines the potential of temporary circulatory support to induce permanent myocardial recovery even in cases of preexisting cardiomyopathy.

Composite risk scores and depression as predictors of competing waiting-list outcomes: the Waiting for a New Heart Study.

We evaluated two composite risk scores, (Heart Failure Survival Score, HFSS; German Transplant Society Score, GTSS), and depression as predictors of mortality and competing waiting-list outcomes [high-urgency transplantation (HU-HTx), elective transplantation, delisting because of clinical improvement] in 318 heart transplant (HTx) candidates (18% women; aged 53 ± 11 years) from 17 hospitals and newly registered with Eurotransplant. Demographic variables and depression (Hospital Anxiety and Depression Scale, HADS) were assessed using questionnaires. Variables to compute HFSS and GTSS, age, medications, and outcomes were provided by Eurotransplant. At 12 months, 33 patients died, 83 received urgent HTx, 30 elective HTx, and 17 were delisted because of improvement. Applying cause-specific Cox regressions, only the HFSS was significantly associated with 1-year mortality [HR = 0.64 (95% CI = 0.43-0.95), P = 0.029]. The GTSS was the strongest predictor of HU-HTx [HR= 1.02 (95% CI = 1.01-1.02), P < 0.001]. Low depression scores contributed significantly to clinical improvement, even after adjusting for age and risk scores [HADS: HR = 0.12 (95% CI = 0.02-0.89), P = 0.039]. These findings confirm the usefulness of composite risk scores for the prediction of mortality and HU-HTx, validating both scores for their intended use. The finding that depression was an independent predictor of the waiting-list outcome clinical improvement suggests that considering patients' psychological attributes in addition to their medical characteristics is advisable.

Asymptomatic infection with novel influenza A/H1N1 virus in a heart transplant recipient.

The spectrum of manifestations and management of the novel influenza A/H1N1 virus in transplanted patients is currently of major concern. Asymptomatic infections are less common yet important for spreading of the virus and thus affect containment measures. To our knowledge, there are no reports of asymptomatic infections with influenza A/H1N1 in immunosuppressed patients. We present the first case of a young heart transplant recipient who remained asymptomatic despite positive polymerase chain reaction (PCR) after exposure to individuals with influenza A/H1N1.

Reduction of cyclosporine after introduction of mycophenolate mofetil improves chronic renal dysfunction in heart transplant recipients--the IMPROVED multi-centre study.

AIMS: This comparative prospective multi-centre study evaluated efficacy and safety of cyclosporine A downtitration in heart transplant recipients with chronic renal dysfunction potentially attributable to cyclosporine (n=161). METHODS: In the intervention arm (n=109, recruited from 9 centres), mycophenolate mofetil was introduced de novo or substituting azathioprine, followed by cyclosporine reduction (target trough levels 2-4 microg/ml and 50 ng/ml, respectively). In controls (n=52, recruited from 1 centre), immunosuppression remained unchanged. Renal function was recorded twelve, six, and three months before, and throughout the eight-month study period. RESULTS: At study entry, cyclosporine trough levels and renal function parameters were comparable. At study end, mean+/-SD cyclosporine in the intervention arm was 57+/-24 vs. 116+/-36 ng/ml in controls. During the study, creatinine decreased by 23.3+/-50.7 micromol/l (P<0.0001) in the intervention arm but increased by 7.3+/-46.9 micromol/l (P=0.992) in controls (P=0.0001 for comparison between groups). A creatinine reduction of at least 20% was found in 35% of subjects of the intervention arm but only in 4% in the control arm (P<0.0001 for comparison between groups). Improvement in renal function was not weakened after adjustment for baseline characteristics in multiple regression analysis. Renal function improved in strata of creatinine entry values from 150 to 310 micromol/l, regardless of the presence of diabetes. Myocardial biopsies at target levels for cyclosporine and mycophenolate mofetil showed three reversible subclinical rejection episodes. CONCLUSIONS: Cyclosporine downtitration improved renal dysfunction in diabetic and non-diabetic heart transplant recipients across a wide range of creatinine levels. The long-term benefit of this strategy deserves further study.

Protection of lung tissue against ischemia/reperfusion injury by preconditioning with inhaled nitric oxide in an in situ pig model of normothermic pulmonary ischemia.

Topical administration of nitric oxide (NO) by inhalation is currently used as therapy in various pulmonary diseases, but preconditioning with NO to ameliorate lung ischemia/reperfusion (I/R) injury has not been fully evaluated. In this study, we investigated the effects of NO inhalation on functional pulmonary parameters using an in situ porcine model of normothermic pulmonary ischemia. After left lateral thoracotomy, left lung ischemia was maintained for 90 min, followed by a 5h reperfusion period (group I, n = 7). In group II (n = 6), I/R was preceded by inhalation of NO (10 min, 15 ppm). Animals in group III (n = 7) underwent sham surgery without NO inhalation or ischemia. In order to evaluate the effects of NO preconditioning, lung functional and hemodynamic parameters were measured, and the zymosan-stimulated release of reactive oxygen species in arterial blood was determined. Animals in group I developed significant pulmonary I/R injury, including pulmonary hypertension, a decreased pO(2) level in pulmonary venous blood of the ischemic lung, and a significant increase of the stimulated release of reactive oxygen species. All these effects were prevented, or the onset (release of reactive oxygen species) was delayed, by NO inhalation. These results indicate that preconditioning by NO inhalation before lung ischemia is protective against I/R injury in the porcine lung.

Attenuation of reperfusion-induced systemic inflammation by preconditioning with nitric oxide in an in situ porcine model of normothermic lung ischemia.

STUDY OBJECTIVES: Inhalation of nitric oxide (NO) can ameliorate pulmonary ischemia/reperfusion (I/R) injury of the lung in several experimental models, but toxic effects of NO were also reported. Here we investigate whether NO inhalation for a short period prior to surgery is sufficient to prevent symptoms of lung I/R injury, especially the inflammatory response. DESIGN: Using an in situ porcine lung model, normothermic left lung ischemia was maintained for 90 min, followed by a 5-h reperfusion period (group 1, n = 7). In group 2 (n = 6), I/R was preceded by inhalation of NO (10 min, 15 ppm). Animals in group 3 (n = 7) underwent sham surgery without NO inhalation or ischemia. MEASUREMENTS: Oxygenation and hemodynamic parameters were measured as indicators of lung functional impairment. Plasma levels of interleukin (IL)-1beta, IL-6, and transforming growth factor (TGF)-beta1 were determined throughout the I/R maneuver. In addition, tissue macrophages were analyzed by lectin binding. RESULTS: Symptoms of I/R injury (pulmonary hypertension and decreased oxygenation) in group 1 animals were attenuated by NO inhalation. The reperfusion-induced increases of the levels of IL-1beta and IL-6 in plasma were reduced by NO pretreatment. A peak of TGF-beta1 immediately after NO administration was observed in group 2, but not in groups 1 and 3. There was no significant effect of NO on tissue macrophages. CONCLUSION: NO inhalation for a short period prior to lung I/R is sufficient to protect against pulmonary hypertension, impaired oxygenation, and the inflammatory response of pulmonary I/R injury.

Do vitamins C and E attenuate the effects of reactive oxygen species during pulmonary reperfusion and thereby prevent injury?

BACKGROUND: We established an in vivo pig model of standardized lung ischemia to analyze pulmonary reperfusion injury. Enhanced chemiluminescence measurement (CM) allowed immediate quantification of reactive oxygen species (ROS) and subsequent lipid peroxidation. In such model we analyzed efficacy of vitamins C and E to prevent reperfusion injury. METHODS: After left lateral thoracotomy in group I (n = 6), normothermic lung ischemia was maintained for 90 minutes followed by a 5-hour reperfusion period. In group II, animals (n = 6) underwent ischemia as in group I, but received vitamins (preoperative IV bolus C = 1 g, E = 0.75 g, then continuous infusion (125 mg/h) each throughout the study). In Group III, animals (n = 6) underwent sham surgery and served as controls. Hemodynamic variables and gas exchange were assessed. The CM was performed for injury quantification in blood samples and to determine activation of isolated PMNs. The Wilcox rank test was used for statistical analysis. RESULTS: During reperfusion, all animals in group I developed significant pulmonary edema with significant loss of pulmonary function. The addition of vitamins (group II) improved oxygenation and almost abolished pulmonary inflammatory cell infiltration; however, as in group I, pulmonary compliance still tended to decline and the number of circulating leucocytes increased. The CM showed that, compared with group I, vitamins reduced O2- basic release by PMNs significantly (460% to 170%, p < 0.05; control 165%), but could not prevent an increase of free ROS in whole blood similar to group I (443% to 270%, p = ns, control 207%). With regard to lipid peroxidation only a trend of reduction was observed (117% to 105%, p = ns, control 100%). CONCLUSIONS: Differentiated analysis by CM demonstrated that vitamins C and E inhibited PMN activation but were not able to prevent radical production by other sources. This offers a potential explanation why radical scavengers like vitamins only attenuate but ultimately do not prevent reperfusion injury.