Clinical and economic impact of ventricular assist device infections: a real-world claims analysis.

BACKGROUND: VAD therapy has revolutionized the treatment of end-stage heart failure, but infections remain an important complication. The objective of this study was to characterize the clinical and economic impacts of VAD-specific infections. METHODS: A retrospective analysis of a United States claims database identified members ≥ 18 years with a claim for a VAD implant procedure, at least 6 months of pre-implant baseline data, and 12 months of follow-up between 1 June 2016 and 31 December 2019. Cumulative incidence of infection was calculated. Infection and non-infection cohorts were compared regarding mortality, healthcare utilization, and total cost. Regression models were used to identify risk factors associated with infections and mortality. RESULTS: A total of 2,259 patients with a VAD implant were included, with 369 experiencing infection (12-month cumulative incidence 16.1%). Patients with infection were 2.1 times more likely to die (p < 0.001, 95% CI [1.5-2.9]). The mean 12-month total cost per US patient was $354,339 for the non-infection cohort and $397,546 for the infection cohort, a difference of $43,207 (p < 0.0001). CONCLUSIONS: VAD infections were associated with higher mortality, more healthcare utilization, and higher total cost. Strategies to minimize VAD-specific infections could lead to improved clinical and economic outcomes.

First in man evaluation of a novel circulatory support device: Early experience with the Impella 5.5 after CE mark approval in Germany.

BACKGROUND: The Abiomed Impella 5.5 (Danvers, MA) is a newly developed axial flow transaortic cardiac support device mounted on a 9 Fr steering catheter with a 21 Fr pump cannula. Impella 5.5 is intended for longer use and was approved for 30 days in 2018. This study evaluated the first-in-man series at six high-volume mechanical circulatory support centers in Germany after CE approval. METHODS: The first 46 consecutive patients worldwide underwent implantation in six German centers between March 2018 and September 2019 for post-CE approval evaluation. The primary end-point was 30 days and 90 days all-cause mortality. RESULTS: The mean age of patients was 59.0 ± 11.5 years, and 43 (93.4%) were men. Half of the patients had acute on chronic heart failure. The main indication for Impella 5.5 implantation was ischemic cardiomyopathy and acute myocardial infarction (47.8%). The mean support time was 15.5 ± 24.2 days (range 0-164, median 10 days (IQR = 7-19)) with a total of 712 patient-days on support. The 30 days and 90 days survival rates were 73.9% (95% CI: 63.3-88.9%) and 71.7% (95% CI: 60.7-87.1%), respectively. Additionally, 16 patients (34.8%) were weaned from the device for native heart recovery, and 19 (41.3%) were bridged to a durable device. Fifteen patients (32.6%) were mobilized to a chair, and 15 (32.6%) were ambulatory. We only noted one stroke and found no other thromboembolic complications. No aortic valve damage was observed in the study cohort. Finally, seven patients (15.2 %) had pump thrombosis, and nine (19.6 %) underwent device exchange. Sixteen patients (34.8 %) suffered from bleeding requiring transfusions during the whole treatment course. In ten patients (21.7%), the inflow cannula dislocated into the aortic root. CONCLUSIONS: The first version of the Impella 5.5 presents promising early outcomes for patients with acute heart failure and expands the spectrum of available devices. The adverse event profile is favorable for short-term devices. Dislocations have been addressed by design changes. With increasing experience with this device, our study suggests that the indications for use will expand to other cardiac shock etiologies and may improve myocardial recovery and survival in patients with cardiogenic shock.

Improved aftercare in LVAD patients: Development and feasibility of a smartphone application as a first step for telemonitoring.

For the success of the treatment with a left ventricular assist device (LVAD), both adequate self-management by the patient and an optimum level of support from the implanting hospital are crucial. A smartphone application has recently been developed within the framework of a European research project for the close monitoring of LVAD patients in order to improve upon their current aftercare situation. Using this new tool, different relevant parameters (eg, weight, international normalized ratio [INR], medication, LVAD parameters, symptoms, and photos of the driveline exit) can be sent daily or as required to a corresponding clinical application at the hospital for evaluation. The objective of this study was to monitor the functionality, acceptance, and usability of this smartphone application in LVAD patients. Prospective single-center study: in total, 13 patients (60 ± 7 years, 92% male, 1027 ± 653 days after LVAD implantation) were requested to test the application for approx. 4 weeks. At the end of the study, all entered data were evaluated and the patients were questioned regarding the acceptance and the usability. During the study period of mean 34 ± 8 days, a total of 453 data records (mean 35 ± 7 per patient) arrived at the hospital. In addition, a total of 19 photos of the driveline exit site were also sent via smartphone. The clinical application registered a total of 160 conspicuities. These comprised 126 INR deviations (target range 2.3-2.8) and 34 symptoms (mainly nosebleeds). The smartphone application functioned reliably, was well received by the patients and was graded highly for acceptance and usability. The results show that smartphone applications can definitely be used to improve aftercare in LVAD therapy in selected patients. Long-term studies are now needed to investigate the extent to which complications can be prevented, healthcare costs reduced, and quality of life increased.

Requirements for a Telemedicine Center to Monitor LVAD Patients.

E-health, especially telemedicine, has undergone a remarkably dynamic development over the last decade. Most experience is currently in the field of telemedical care for heart failure (HF) patients. However, HF patients with an implanted left-ventricular assist device (LVAD) have been more or less excluded from consistent telemonitoring until now. The majority of complications associated with LVAD therapy occur during the post-implantation phase. Effective outpatient management is therefore the key to improving long-term outcome of LVAD patients. Thereby, implementation of a telemedicine center for close monitoring could play an important role, e.g. through early detection of complications. This study provides insights into structural, staff and spatial requirements for a telemedicine center to monitor the special group of LVAD patients, based on comprehensive literature research and expert interviews.

Development of exercise-related values in heart failure patients supported with a left ventricular assist device.

Following implantation of a left ventricular assist device, the build-up and long-term maintenance of adequate exercise capacity and functional performance become crucial. The aim of this study was to observe the development of exercise-related values at different times, as well as to detect possible influencing factors. We performed a prospective single-centre study: 10 patients (63 years, 100% male, body mass index = 27.5, 100% HeartWare) underwent the following diagnostic tests during cardiac rehabilitation and during two subsequent ambulatory visits: 6-min walking test, handgrip strength test, cardiopulmonary exercise test and Minnesota Living with Heart Failure questionnaire. Mean follow-up was 482 days after left ventricular assist device implantation. Significant improvements could be observed between the end of cardiac rehabilitation and ambulatory visit 1; 6-min walking distance increased from 367 to 449 m (p < 0.01), peak VO2 from 10.0 to 11.9 mL/kg/min (p < 0.05) and peak load from 62.4 to 83.0 W (p < 0.01). However, there were no further improvements between ambulatory visit 1 and ambulatory visit 2. In the long term, a significant mean weight gain of more than 10 kg could be observed (p < 0.01). A negative linear correlation between weight gain and absolute improvement in peak load (r = -0.77, p < 0.01) and peak VO2 (r = -0.75, p < 0.05) could be demonstrated. In conclusion, exercise-related values following left ventricular assist device implantation initially improve significantly. Later, however, no further improvements can be observed. In the long term, pronounced weight gain is conspicuous, concomitant with a significantly lower increase in exercise values of the patients. In the future, both dietary and structured physical activity follow-up interventions should be integrated in patient routines.

Telemonitoring of left-ventricular assist device patients-current status and future challenges.

E-health, especially telemedicine, has undergone a remarkably dynamic development over the past few years. Most experience is currently in the field of telemedical care for heart failure (HF) patients. However, HF patients with an implanted left-ventricular assist device (LVAD) have been more or less excluded from consistent telemonitoring until now. And yet, continual monitoring would be very significant for this patient group because of the complexity of its aftercare, requiring steady control of various parameters (device-related parameters, vital parameters, coagulation parameters, etc.). With timely action, severe and costly complications like pump thromboses and driveline infections could be detected early on or even avoided completely. This paper describes the potential of telemonitoring in LVAD patients, as well as its first clinical implementation according to the available literature. It also describes the requirements for a complete telemonitoring of LVAD patients, facilitating the advancement of this form of continual monitoring to a clinical standard which would increase the quality of aftercare for this very special patient collective enormously.

Effects of pump speed changes on exercise capacity in patients supported with a left ventricular assist device-an overview.

The implantation of left ventricular assist devices (LVAD) has been established as a successful treatment for terminal heart failure (HF) for many years. Patient benefits include significantly improved survival, as well as improved quality of life. However, peak exercise capacity following LVAD implantation remains considerably restricted. This could be due to the predominate use of continuous-flow pumps, which operate at a fixed rotational speed and do not adapt to exercise conditions. Therefore, current research is focused on whether, and to what extent, adaptations in pump speed can influence and improve patient exercise capacity. We performed a systematic PubMed literature search on this topic, and found 11 relevant studies with 161 patients. Exercise time, peak work load, total cardiac output (TCO), peak oxygen consumption (peak VO2) and, if available, values at the anaerobic threshold (AT) were all taken into consideration. Possible complications were documented. This paper aims to compare the results from these studies in order to discuss the effects of pump speed adaptations on exercise capacity.

Changes in Total Cardiac Output and Oxygen Extraction During Exercise in Patients Supported With an HVAD Left Ventricular Assist Device.

Following implantation of a left ventricular assist device (LVAD), acceptable functional performance is now being achieved; however, peak VO2 and peak work load (watts) remain considerably limited. Maximum physical capacity is essentially dependent on generated cardiac output (CO) and arteriovenous oxygen difference (avDO2 ). We investigated the changes in CO and avDO2 during exercise in LVAD patients with an HVAD pump (HeartWare Inc., Framingham, MA, USA). Approximately 6 weeks after implantation, 20 patients (100% male, 60.8 ± 7.3 years old, BMI 25.7 ± 3.3) underwent a six-minute walk test (6MWT), a cardiopulmonary exercise test (CPET), and noninvasive hemodynamic measurement. The mean six-minute walking distance (6MWD) was 403 m (68% of predicted), and mean peak VO2 was 10.9 mL/kg/min (39% of predicted). Mean total CO improved from 3.8 L at rest to 7.0 L at maximum exercise. The mean avDO2 increased from 7.4 mL/dL (44% of oxygen content) at rest to 13.2 mL/dL (75% of oxygen content) at maximum exercise. There was a significant increase in both total CO (P < 0.01) and avDO2 (P < 0.05) between rest and sub-maximum exercise. As exercise levels increased, however, no further significant changes were achieved. Long-term studies, especially in combination with exercise programs, would be desirable in order to observe the development of these parameters.

Exercise Capacity and Functional Performance in Heart Failure Patients Supported by a Left Ventricular Assist Device at Discharge From Inpatient Rehabilitation.

Adequate physical and functional performance is an important prerequisite for renewed participation and integration in self-determined private and (where appropriate) professional lives following left ventricular assist device (LVAD) implantation. During cardiac rehabilitation (CR), individually adapted exercise programs aim to increase exercise capacity and functional performance. A retrospective analysis of cardiopulmonary exercise capacity and functional performance in LVAD patients at discharge from a cardiac rehabilitation program was conducted. The results from 68 LVAD patients (59 males, 9 females; 55.9 ± 11.7 years; 47 HVAD, 2 MVAD, 15 HeartMate II, 4 HeartMate 3, and 4 different implanting centers) were included in the analysis. Exercise capacity was assessed using a cardiopulmonary exercise test on a bicycle ergometer (ramp protocol; 10 W/min). The 6-min walk test was used to determine functional performance. At discharge from CR (53 ± 17 days after implantation), the mean peak work load achieved was 62.2 ± 19.3 W (38% of predicted values) or 0.79 ± 0.25 W/kg body weight. The mean cardiopulmonary exercise capacity (relative peak oxygen uptake) was 10.6 ± 5.3 mL/kg/min (37% of predicted values). The 6-min walk distance improved significantly during CR (325 ± 106 to 405 ± 77 m; P < 0.01). No adverse events were documented during CR. The results show that, even following LVAD implantation, cardiopulmonary exercise capacity remains considerably restricted. In contrast, functional performance, measured by the 6-min walk distance, reaches an acceptable level. Light everyday tasks seem to be realistically surmountable for patients, making discharge from inpatient rehabilitation possible. Long-term monitoring is required in order to evaluate the situation and how it develops further.

Hemodynamic analysis of outflow grafting positions of a ventricular assist device using closed-loop multiscale CFD simulations: Preliminary results.

Subclavian arteries are a possible alternate location for left ventricular assist device (LVAD) outflow grafts due to easier surgical access and application in high risk patients. As vascular blood flow mechanics strongly influence the clinical outcome, insights into the hemodynamics during LVAD support can be used to evaluate different grafting locations. In this study, the feasibility of left and right subclavian artery (SA) grafting was investigated for the HeartWare HVAD with a numerical multiscale model. A 3-D CFD model of the aortic arch was coupled to a lumped parameter model of the cardiovascular system under LVAD support. Grafts in the left and right SA were placed at three different anastomoses angles (90°, 60° and 30°). Additionally, standard grafting of the ascending and descending aorta was modelled. Full support LVAD (5l/min) and partial support LVAD (3l/min) in co-pulsation and counter-pulsation mode were analysed. The grafting positions were investigated regarding coronary and cerebral perfusion. Furthermore, the influence of the anastomosis angle on wall shear stress (WSS) was evaluated. Grafting of left or right subclavian arteries has similar hemodynamic performance in comparison to standard cannula positions. Angularity change of the graft anastomosis from 90° to 30° slightly increases the coronary and cerebral blood flow by 6-9% while significantly reduces the WSS by 35%. Cannulation of the SA is a feasible anastomosis location for the HVAD in the investigated vessel geometry.

Regulation of cyclic adenosine monophosphate release by selective ß2-adrenergic receptor stimulation in human terminal failing myocardium before and after ventricular assist device support.

BACKGROUND: Response to catecholamines is blunted in terminal heart failure due to ß-receptor downregulation and uncoupling from adenylyl cyclase (AC). Improved myocardial responsiveness to catecholamines after ventricular assist device (VAD) support is associated with upregulation of ß1-adrenergic receptors (ß1-ARs). Little is known about the regulation of AC and ß2-AR coupling after VAD; moreover ß2-AR stimulation during VAD was claimed to induce myocardial recovery. METHODS: We analyzed in VAD-supported human myocardium the regulation of AC activity upon ß1-AR and selective ß2-AR stimulation in 8 non-failing hearts (NF) and 17 paired samples of VAD patients. AC messenger RNA was measured by TaqMan. AC was stimulated via ß2-AR using clenbuterol (ß2-AR agonist) and bisoprolol (ß1-AR blocker). Organ bath experiments were done with trabeculae from both ventricles. Samples were stratified according to chronic or acute heart failure history. RESULTS: Isoprenaline-induced AC activity was downregulated (p < 0.001) pre-VAD and increased significantly (p < 0.05) after unloading (mean ± standard deviation pmole/mg/min) in NF (47.9 ± 14.9), pre-VAD (24.35 ± 13.3), and post-VAD (50.04 ± 50.25). Forskolin stimulation revealed significant (p < 0.05) upregulation of AC activity during VAD, especially in acutely failing hearts (NF, 192.1 ± 68.7; pre-VAD, 191.1 ± 60.4; post-VAD, 281.5 ± 133). However, forskolin stimulation relative to isoprenaline-induced inotropy remained reduced before and after VAD compared with NF. The selective stimulation of ß2-AR did not reveal influence of VAD support on ß2-AR-AC coupling. Stimulation of ventricular trabeculae by > 100 µmole/liter clenbuterol revealed negative inotropic responses. CONCLUSIONS: VAD does not influence ß2-AR coupling to AC stimulation. Elevated response to catecholamines after VAD support is influenced by ß1-AR upregulation and modulation of AC activity. Restoration of ß-adrenergic responsiveness was restricted to acutely failing hearts.

Global gene expression analysis in nonfailing and failing myocardium pre- and postpulsatile and nonpulsatile ventricular assist device support.

Mechanical unloading by ventricular assist devices (VAD) leads to significant gene expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD support and its relationship to nonfailing hearts (NF). In addition no data are available for the transcriptome regulation during nonpulsatile VAD support. Therefore we analyzed the gene expression patterns of 30 paired samples from VAD-supported (including 8 nonpulsatile VADs) and 8 nonfailing control hearts (NF) using the first total human genome array available. Transmural myocardial samples were collected for RNA isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data were analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). We found 352 transcripts were differentially regulated between samples from VAD implantation and NF, whereas 510 were significantly regulated between VAD transplantation and NF (paired t-test P < 0.001, fold change >or=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD support. Unsupervised hierarchical clustering of paired VAD and NF samples revealed separation of HF and NF samples; however, individual differentiation of VAD implantation and VAD transplantation was not accomplished. Clustering of pulsatile and nonpulsatile VAD did not lead to robust separation of gene expression patterns. During VAD support myocardial gene expression changes do not indicate reversal of the HF phenotype but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and nonpulsatile VAD-supported hearts did not provide evidence for a pump mode-specific transcriptome pattern.

DuraHeart magnetically levitated centrifugal left ventricular assist system for advanced heart failure patients.

The implantable left ventricular assist system (LVAS) using pulsatile pump technology has become an established therapeutic option for advanced heart failure patients. However, there have been technological limitations in some older designs, including a high incidence of infection and mechanical failures associated with moving parts, and the large size of both implantable pump and percutaneous cable. A smaller rotary blood pump emerged as a possible alternative to a large pulsatile pump to overcome some of these limitations. The technological advancement that defines the third-generation LVAS was the elimination of all mechanical contacts between the impeller and the drive mechanism. The DuraHeart LVAS is the world's first third-generation implantable LVAS to obtain market approval (CE-mark), which combines a centrifugal pump and active magnetic levitation. The initial clinical experience with the DuraHeart LVAS in Europe demonstrated that it provided significantly improved survival (85% at 6 months and 79% at 1 year), reduced adverse event rates and long-term device reliability (freedom from device replacement at 2 years: 96 +/- 3%) over pulsatile LVAS.

Reconstructive surgery for an akinetic anterior ventricular wall in ischemic cardiomyopathy.

BACKGROUND: The purpose of this prospective study is to analyze the postoperative outcome after only left ventricular reconstruction (LVR) versus LVR combined with coronary artery bypass grafting (CABG) and/or mitral valve (MV) procedure in ischemic cardiomyopathy (ICM) as a result of an akinetic anterior ventricular wall. METHODS AND RESULTS: Nineteen patients underwent only LVR, and 37 underwent a concomitant LVR procedure. In both groups, New York Heart Association (NYHA) classification improved significantly from 3.5 +/- 0.6 to 2.2 +/- 0.5 (LVR group) and 3.4 +/- 0.7 to 2.5 +/- 0.5 (combined LVR group). Ejection fraction improved significantly from 25.1 +/- 3.2 to 35.3 +/- 4.5% in the LVR group and 28.1 +/- 2.2 to 37.6 +/- 5.5% in the combined LVR group. Cardiac index improved significantly from 1.8 +/- 0.6 to 2.3 +/- 0.5 l/min/m2 in the LVR group and 1.6 +/- 0.4 to 2.2 +/- 0.6 l/min/m2 in the combined LVR group. An additional concomitant procedure increased the mortality rate only slightly. The overall 1- and 5-year actuarial survival rates were 90% and 75% in the LVR group and 80% and 70% in the combined LVR group. CONCLUSIONS: The LVR for akinetic ventricular wall shows very satisfactory early and long-term results. The LVR, with or without concomitant procedures, has considerable benefits for operative therapy.

Long-term survival after cardiac retransplantation: a single-center experience.

Cardiac retransplantation is controversial therapy because of a chronic shortage of donor hearts. We retrospectively reviewed short- and long-term outcomes after cardiac retransplantation. Between February 1989 and December 2004, 28 cases of cardiac retransplantation were performed. Indications for retransplantation were primary graft failure (PGF) in 11 patients (39.3%), intractable acute cardiac rejection (IACR) in 4 (14.3%), and coronary allograft vasculopathy (CAV) in 13 (46.4%). The patients had been supported with prolonged cardiopulmonary bypass (CPB) (n = 3), IABP (n = 1), intravenous inotropic support (n = 7), ECMO (n = 3), and VAD (n = 4). Ten patients had no inotropic support. Eight patients died within 30 days postoperatively. The causes of early death were acute rejection (n = 3 ; 37%), MOF (n = 3 ; 37%), PGF (n = 1 ; 13%), and right ventricular failure (n = 1 ; 13%). The causes of late death in 8 other patients were acute rejection (n = 4 ; 50%), CAV (n = 2 ; 25%), MOF (n = 1 ; 13%), and infection (n = 1 ; 13%). The 1-, 5-, 10-, and 15-year survivals were 78.5, 68.4, 54.5, and 38.3%, respectively, for primary cardiac transplantation, and 46.4, 40.6, 32.5, and 32.5% for cardiac retransplantation (P = 0.003). Acute cardiac rejection was the most common cause of death (43.8%). Thirty-day and 1-year survivals of IACR, PGF, and CAV were 50.0/0, 63.6/45.5, and 84.6/68.4%, respectively. Long-term survival after retransplantation was acceptable for patients with CAV and PGF, however, we should select patients carefully if the indication for retransplantation is IACR because of the poor outcome.

Implantation of active fixation leads in coronary veins for left ventricular stimulation: report of five cases.

BACKGROUND: Securing transvenous left ventricular (LV) pacing leads without an active fixation mechanism in proximal coronary vein (CV) segments is usually challenging and frequently impossible. We investigated how active fixation leads can be safely implanted in this location, how to avoid perforating the free wall of the CV, and how to recognize and respond to perforations. MATERIALS AND METHODS: In five patients with no alternative to LV pacing from proximal CV segments, 4 Fr SelectSecure (Medtronic, Minneapolis, MN, USA) leads, which have a fixed helix, were implanted through a modified 6 Fr guide catheter with a pre-shaped tip (Launcher, Medtronic). RESULTS: Active fixation leads were successfully implanted in proximal CVs in five patients. There were no complications. Acute and chronic pacing thresholds were comparable to those of conventional CV leads. The pre-shaped guide catheter tip remains in close proximity to the myocardial aspect of the CV, directing the lead helix toward a safe implantation site. CONCLUSIONS: If only proximal CV pacing sites are available, 4 Fr SelectSecure leads can be safely implanted through a modified Launcher guide catheter, avoiding more invasive implantation techniques. Other than venous stenting or implantation of leads with retractable tines, SelectSecure leads are expected to remain extractable.

Three cases of orthotopic heart transplantation for arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy that primarily affects the heart muscle in the right ventricle. The ventricular muscle is replaced by fatty or fibrous tissue in a diffuse or spotty process. We performed orthotopic heart transplantations in 3 patients and all patients are alive. When ARVC has progressed to heart failure in the right or left ventricles, orthotopic heart transplantation is an effective therapeutic option.