UNASSIGNED: Selected patients with advanced heart failure ineligible for heart transplantation could benefit from left ventricular assist device therapy as \'destination therapy\'. There is evidence of the efficacy of destination therapy; however, it is not currently commissioned within the United Kingdom National Health Service due to the lack of economic evidence.
UNASSIGNED: What is the clinical and cost-effectiveness of a left ventricular assist device compared to medical management for patients with advanced heart failure ineligible for heart transplantation (destination therapy)?
UNASSIGNED: A systematic review of evidence on the clinical and cost-effectiveness of left ventricular assist devices as destination therapy was undertaken including, where feasible, a network meta-analysis to provide an indirect estimate of the relative effectiveness of currently available left ventricular assist devices compared to medical management. For the systematic reviews, data sources searched (up to 11 January 2022) were Cochrane CENTRAL, MEDLINE and EMBASE via Ovid for primary studies, and Epistemonikos and Cochrane Database of Systematic Reviews for relevant systematic reviews. Trial registers were also searched, along with data and reports from intervention-specific registries. Economic studies were identified in EconLit, CEA registry and the NHS Economic Evaluation Database (NHS EED). The searches were supplemented by checking reference lists of included studies. An economic model (Markov) was developed to estimate the cost-effectiveness of left ventricular assist devices compared to medical management from the United Kingdom National Health Service/personal social service perspective. Deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. Where possible, all analyses focused on the only currently available left ventricular assist device (HeartMate 3TM, Abbott, Chicago, IL, USA) in the United Kingdom.
UNASSIGNED: The clinical effectiveness review included 134 studies (240 articles). There were no studies directly comparing HeartMate 3 and medical management (a randomised trial is ongoing). The currently available left ventricular assist device improves patient survival and reduces stroke rates and complications compared to earlier devices and relative to medical management. For example, survival at 24 months is 77% with the HeartMate 3 device compared to 59% with the HeartMate II (MOMENTUM 3 trial). An indirect comparison demonstrated a reduction in mortality compared to medical management [relative risk of death 0.25 (95% confidence interval 0.13 to 0.47); 24 months; this study]. The cost-effectiveness review included 5 cost analyses and 14 economic evaluations covering different generations of devices and with different perspectives. The reported incremental costs per quality-adjusted life-year gained compared to medical management were lower for later generations of devices [as low as £46,207 (2019 prices; United Kingdom perspective; time horizon at least 5 years)]. The economic evaluation used different approaches to obtain the relative effects of current left ventricular assist devices compared to medical management from the United Kingdom National Health Service/personal social service perspective. All gave similar incremental cost-effectiveness ratios of £53,496-58,244 per quality-adjusted life-year gained - lifetime horizon. Model outputs were sensitive to parameter estimates relating to medical management. The findings did not materially differ on exploratory subgroup analyses based on the severity of heart failure.
UNASSIGNED: There was no direct evidence comparing the clinical effectiveness of HeartMate 3 to medical management. Indirect comparisons made were based on limited data from heterogeneous studies regarding the severity of heart failure (Interagency Registry for Mechanically Assisted Circulatory Support score distribution) and possible for survival only. Furthermore, the cost of medical management of advanced heart failure in the United Kingdom is not clear.
UNASSIGNED: Using cost-effectiveness criteria applied in the United Kingdom, left ventricular assist devices compared to medical management for patients with advanced heart failure ineligible for heart transplant may not be cost-effective. When available, data from the ongoing evaluation of HeartMate 3 compared to medical management can be used to update cost-effectiveness estimates. An audit of the costs of medical management in the United Kingdom is required to further decrease uncertainty in the economic evaluation.
UNASSIGNED: This study is registered as PROSPERO CRD42020158987.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128996) and is published in full in Health Technology Assessment; Vol. 28, No. 38. See the NIHR Funding and Awards website for further award information.
The majority of patients with advanced heart failure would be unsuitable for heart transplantation due to their age and comorbidities but selected patients could benefit from a left ventricular assist device. Left ventricular assist device therapy for such patients is known as ‘destination therapy’. This is a long-term therapy that involves implanting a battery-powered pump to support the patient’s heart. The purpose of this project was to collect and assess the research evidence on the effectiveness of left ventricular assist devices when used for destination therapy, and to estimate value for money compared to medical management from the United Kingdom National Health Service/personal social service perspective. This research identified that the currently available left ventricular assist device improves patient survival as well as reducing stroke rates and complications compared to earlier devices and relative to medical management. However, there is uncertainty in the evidence due to the absence of studies directly comparing the current device to medical therapy alone. An ongoing clinical trial is currently assessing this. It also means there is uncertainty about whether left ventricular assist devices could provide value for money as determined currently for the United Kingdom National Health Service.

Left ventricular assist devices (LVADs) are increasingly implanted in patients with advanced heart failure. Currently, LVAD care is predominantly concentrated at specialized tertiary care hospitals. However, the increasing workload and logistical burden for implanting centres pose significant challenges to accessing care for individual patients in remote areas. An emerging approach to LVAD patient management is the use of a shared care model (SCM), which facilitates collaboration between implanting centres and local non-implanting hospitals. This scoping review explores and synthesizes the current scientific evidence on the use of SCMs in LVAD care management. Eligible studies were identified in EMBASE, PubMed MEDLINE, Web of Science, Cochrane and Google Scholar. Findings were synthesized in accordance with PRISMA-ScR guidelines. Of the 950 records screened, five articles met the inclusion criteria. Four review articles focused on the proposed benefits and challenges of using SCMs. Main benefits included improved patient satisfaction and continuity of care. Important challenges were initial education of non-implanting centre staff and maintaining competency. One prospective study showed that absence of LVAD-specific care was associated with impaired survival and higher rates of pump thrombosis and LVAD-related infections. The use of SCMs is a promising approach in the long-term management of LVAD patients. However, sufficient evidence about the impact of SCMs on patients and the healthcare system is not currently available. Standardized protocols based on prospective studies are needed to develop safe and effective shared care for LVAD patients.

With changes in the heart transplant allocation system in the United States, the use of left ventricular device therapy (LVAD) as a bridge to transplant has decreased. Currently, one of the primary reasons to implant a device is for patient support until they can lose weight to qualify for transplant. This paper reviews the outcomes of various weight loss strategies for patients with LVADs including weight reduction surgery and cardiac rehab. Additionally, results of the use of GLP1 agonists on weight loss in general and in heart failure patients is reviewed. Finally, because of the unique issues involving exercise for patients with LVADs, we review safe exercise techniques with instructions for patients.

The function of the right ventricle (RV) is to drive the forward flow of blood to the pulmonary system for oxygenation before returning to the left ventricle. Due to the thin myocardium of the RV, its function is easily affected by decreased preload, contractile motion abnormalities, or increased afterload. While various etiologies can lead to changes in RV structure and function, sudden changes in RV afterload can cause acute RV failure which is associated with high mortality. Early detection and diagnosis of RV failure is imperative for guiding initial medical management. Echocardiographic findings of reduced tricuspid annular plane systolic excursion (<1.7) and RV wall motion (RV S\' <10 cm/s) are quantitatively supportive of RV systolic dysfunction. Medical management commonly involves utilizing diuretics or fluids to optimize RV preload, while correcting the underlying insult to RV function. When medical management alone is insufficient, mechanical circulatory support (MCS) may be necessary. However, the utility of MCS for isolated RV failure remains poorly understood. This review outlines the differences in flow rates, effects on hemodynamics, and advantages/disadvantages of MCS devices such as intra-aortic balloon pump, Impella, centrifugal-flow right ventricular assist devices, extracorporeal membrane oxygenation, and includes a detailed review of the latest clinical trials and studies analyzing the effects of MCS devices in acute RV failure.

BACKGROUND: Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional capacity and quality of life. However, two major complications compromise this patient population\'s outcomes: thrombosis and bleeding. Despite technological innovations and better hemocompatibility, these devices alter the rheology, triggering the coagulation cascade and, therefore, require antithrombotic therapy. Anticoagulation and antiplatelet therapies represent the current standard of care. Still, inconsistency in the literature exists, especially whether antiplatelet therapy is required, whether direct oral anticoagulants can replace vitamin K antagonists and even whether phosphodiesterase type 5 inhibitors with their antithrombotic effects could be added to the regimen of anticoagulation.
METHODS: We will perform a living systematic review with network meta-analysis and indirect comparison between current antithrombotic therapies, which have and have not been directly compared within clinical trials and observational studies. We will systematically search the following electronic sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE). We will exclusively examine studies published in English from 2016 to the present. Studies conducted before 2016 will be omitted since our primary focus is evaluating continuous flow devices. Two independent reviewers will assess the articles by title, abstract and full text; any disagreement will be resolved through discussion, and a third reviewer will be involved if necessary. The Cochrane Risk of Bias tool will be used to assess the risk of bias. We will then conduct a pairwise meta-analysis; if the assumption of transitivity is satisfied, we will proceed with network meta-analysis using Bayesian methodology.
BACKGROUND: Formal ethical approval is not required as no primary data are collected. This systematic review and network meta-analysis will delineate the risks of stroke, thromboembolic events, pump thrombosis, gastrointestinal bleeding and mortality in patients equipped with LVADs who are subjected to various antithrombotic regimens. The findings will be disseminated via a peer-reviewed publication and presented at conference meetings. This will enhance clinical practice and guide future research on anticoagulation strategies within this distinct patient cohort.
UNASSIGNED: CRD42023465288.

BACKGROUND: Evidence on infection risk factors is scarce, and precise localization of the site of infection and its treatment remain clinically challenging.
OBJECTIVE: This study aimed to map the recommendations for adult patients undergoing left ventricular assist device implantation.
METHODS: This is a scoping review, registered in the Open Science Framework under DOI10.17605/OSF.IO/Q76B3(https://osf.io/q76b3/).
METHODS: This is a scoping review limited to the period between 2015 and 2022.The results of this scoping review are discussed and presented separately in 3 articles. This second paper synthesizes research evidence on the risk factors, diagnostic methods and treatment of infection in adult patients undergoing left ventricular assist device implantation.
RESULTS: The initial searches identified 771 studies. Sixty-nine patients met the eligibility criteria and were included in the scoping review. Forty-three articles addressing the risk factors, diagnosis and treatment of infection were included to answer the questions of this review.
CONCLUSIONS: Obesity has been shown to be the most common risk factor for the described process of infection by left ventricular assist devices.18F-fluorodeoxyglucose positron emission tomography showed high sensitivity in detecting cardiac device infection, and labeled leukocyte or gallium citrate-67 scintigraphy showed high specificity for left ventricular assist device infections; therefore, it can help differentiate infection from inflammation, particularly in patients with equivocal fluorodeoxyglucose positron emission tomography. Also, this review brings and discusses the limitations and strengths of diagnostic tests, the knowledge regarding the risk factors for left ventricular assist device infection, the therapeutic heterogeneity, the methodological issues of the studies, and the vast opportunity for future research on left ventricular assist device.
CONCLUSIONS: Ventricular assist device professionals should evaluate risk factors prior to device implantation and periodically.18F-fluorodeoxyglucose positron emission tomography should be considered as diagnostic tool in detecting superficial and deep driveline infections. Early treatment, including chronic suppressive therapy and serial surgical debridement, combined with driveline exteriorization and delayed driveline relocation may constitute a potential therapeutic strategy for deep driveline infections.

OBJECTIVE: This systematic review aims to assess the comparative effectiveness and safety of temporary mechanical circulatory support (MCS) devices in various subgroups of patients with acute cardiogenic shock, providing insights for personalized clinical decision-making.
METHODS: We conducted a comprehensive search across major databases to identify studies that reported on the use of temporary MCS devices like TandemHeart, Impella, and VA-ECMO in acute cardiogenic shock. Special attention was given to subgroup analyses based on etiologies of shock, patient demographics, and comorbid conditions.
RESULTS: Our analysis revealed that while devices like TandemHeart and Impella offer significant hemodynamic support, their effectiveness and safety profiles vary across different patient subgroups. VA-ECMO demonstrated the highest flow rates and potential for mortality benefits but requires careful management due to associated risks. The lack of randomized controlled trials in specific patient subgroups highlights a gap in the current literature, underscoring the need for targeted research.
CONCLUSIONS: The review underscores the necessity of a personalized approach in selecting temporary MCS devices for patients with acute cardiogenic shock, guided by specific patient characteristics and clinical scenarios. Future research should focus on addressing the identified evidence gaps through well-designed studies that provide robust subgroup-specific data, enabling clinicians to optimize treatment strategies and improve patient outcomes in this critical care context.

OBJECTIVE: Recent reports of myocardial recovery after mechanical unloading with left ventricular assist devices (LVADs) have challenged the prevailing notion that end-stage heart failure (HF) is irreversible. To improve our understanding of this phenomenon, we comprehensively analysed the structural, functional, and energetic changes in failing human cardiomyocytes after LVAD implantation.
METHODS: Based on a prospectively registered protocol (PROSPERO-CRD42022380214), 30 eligible studies were identified from 940 records with a pooled population of 648 patients predominantly with non-ischaemic cardiomyopathy.
RESULTS: LVAD led to a substantial regression in myocyte size similar to that of donor hearts (standardised mean difference, -1.29; p<0.001). The meta-regression analysis revealed that HF duration was a significant modifier on the changes in myocyte size. There were some suggestions of fibrosis reversal (-5.17%; p=0.009); however, this was insignificant after sensitivity analysis. Developed force did not improve in cardiac trabeculae (n=5 studies); however, non-physiological isometric contractions were tested. At the myocyte level (n=4 studies), contractile kinetics improved where the time-to-peak force reduced by 41.7%-50.7% and time to 50% relaxation fell by 47.4%-62.1% (p<0.05). Qualitatively, LVAD enhanced substrate utilisation and mitochondrial function (n=6 studies). Most studies were at a high risk of bias.
CONCLUSIONS: The regression of maladaptive hypertrophy, partial fibrosis reversal, and normalisation in metabolic pathways after LVAD may be a testament to the heart\'s remarkable plasticity, even in the advanced stages of HF. However, inconsistencies exist in force-generating capabilities. Using more physiological force-length work-loop assays, addressing the high risks of bias and clinical heterogeneity are crucial to better understand the phenomenon of reverse remodelling.

Pulmonary hypertension (PH) with high pulmonary vascular resistance (PVR) is a very often diagnosed contraindication for orthotopic heart transplantation (OHT). It is a direct consequence of left ventricle failure characterized by high diastolic pressure obstructing the collection of blood from the pulmonary vessels. The occurrence of this situation grows with the increasing time of waiting for OHT, and with the progression of heart failure. Mechanical circulatory support (MCS) devices, particularly left ventricular assist devices (LVADs), have emerged as pivotal interventions for patients with fixed PH, offering a potential bridge to transplantation. The pathophysiological impact of PH in heart transplant candidates is profound, as it is associated with increased perioperative risk and heightened mortality post-transplantation. The selection of heart transplant candidates thus mandates a careful evaluation of PH, with an emphasis on distinguishing between reversible and fixed forms of the condition. Reversible PH can often be managed with medical therapies; however, fixed PH presents a more daunting challenge, necessitating more aggressive interventions like MCS. Patients are supported with LVADs until evidence of pulmonary afterload reversal is evident and then can be considered for heart transplantation. However, in those who are non-responders or have complications while being supported, their option for transplant is revoked. Despite these advancements, the heterogeneity of MCS devices and their mechanisms of action necessitates a nuanced understanding of their efficacy.

BACKGROUND: Pulmonary hypertension (PH) poses a significant challenge in the selection of candidates for heart transplantation, impacting their eligibility and post-transplant outcomes. Mechanical circulatory support (MCS) devices, particularly left ventricular assist devices (LVADs), have emerged as a therapeutic option to manage PH in this patient population. This systematic review aims to evaluate the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates.
METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify studies that evaluated the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates. Data on pulmonary vascular resistance, PH reversal, heart transplant eligibility, and post-transplant outcomes were extracted and synthesized.
RESULTS: The review included studies that demonstrated the potential of MCS devices, especially LVADs, to significantly reduce pulmonary vascular resistance and reverse fixed pulmonary hypertension in heart transplant candidates. These findings suggest that MCS devices can improve transplant eligibility and may positively impact post-transplant survival rates. However, the literature also indicates a need for further comparative studies to optimize MCS device selection and treatment protocols.
CONCLUSIONS: MCS devices, particularly LVADs, play a crucial role in the management of fixed pulmonary hypertension in heart transplant candidates, improving their eligibility for transplantation and potentially enhancing post-transplant outcomes. Future research should focus on comparative effectiveness studies to guide clinical decision-making and optimize patient care in this challenging clinical scenario.