The following are summary points to remember from this review article on left ventricular assist devices (LVADs) for lifelong support:

1. Patients not in cardiogenic shock at the time of LVAD implant enjoy survival that is competitive with heart transplantation out to about 2 years.
2. There are five clinical profiles for LVAD patients. These include: a) normal resting hemodynamics (central venous pressure [CVP] 3-12 mm Hg, pulmonary capillary wedge pressure [PCWP] 8-18 mm Hg); b) right HF (elevated CVP, normal PCWP); c) biventricular failure/fluid overload (elevated CVP and PCWP); d) left HF (normal CVP, elevated PCWP); and e) hypovolemia (low CVP and PCWP). Only 40-60% of patients had “normal” hemodynamics (CVP <12 mm Hg and PCWP <18 mm Hg) at their set speed.
3. Current clinical guidelines support the use of an echocardiographic ramp test to set pump speed. The HeartMate II has a linear relationship between pump speed and LV end-diastolic diameter (LVEDD) at all speeds. In contrast, the HVAD seems to provide minimal unloading until the aortic valve is closed, after which there is rapid unloading. Changes in LV and right ventricular (RV) shape may differ between devices due to the effects of pump position. Specifically, the subdiaphragmatic position of the HeartMate II pulls the apex inferiorly, while the intrapericardial position of the HVAD pushes the apex upwards. These tensile effects may directly alter LV shape, independent of those from augmented unloading at faster speeds, particularly at the base of the heart where LVEDD is measured. Investigations into such geometric differences are ongoing, and their clinical effects are uncertain.
4. Adverse events (AEs) associated with LVADs can be classified into three broad categories: a) Those intrinsic to the pump and its constituents (pump malfunction, controller faults, driveline faults, and short-to-shield malfunctions), b) those that are solely patient-related, and develop due to the liability of the native heart (arrhythmias, valvular insufficiency, and RV failure), and c) those that arise due to the pump-patient interface (acquired von Willebrand’s disease, infection, stroke, and pump thrombosis). The most common AEs within the first year of pump implant are, in declining frequency, bleeding, infection, arrhythmia, respiratory failure, and stroke. One-year survival free of any major AEs is only 30%.
   • RV failure, defined as the need for prolonged inotropic support or the temporary use of an RV assist device (RVAD), occurs in 10-40% of LVAD implants, and can lead to longer hospital length of stay and a higher risk of perioperative death. Late-onset RV failure, occurring months after implant, has emerged as a new clinical challenge, one that is just as difficult to treat and associated with poor survival and quality of life. Those individuals with poor RV hemodynamics (RV stroke work index <250 mm Hg · ml/m², CVP/PCW >0.63, or pulmonary artery pulsatility index <2.0) or echocardiographic evidence of severe RV dysfunction (severe RV enlargement, poor tricuspid plane excursion, reduced peak longitudinal strain) are likely to need prolonged inotropes or an RVAD, and may not be the best candidates for a lifelong LVAD.
   • Bleeding in continuous-flow LVAD patients is associated with development of acquired von Willebrand’s disease, similar to that seen in Heyde syndrome. The shear forces in the blood created by the impeller results in large multimeric forms of von Willebrand factor to unfurl, exposing them to cleavage by the serine protease ADAMTS-13. The resultant von Willebrand factor particles are too small to adhere to sites of vascular trauma or to bind platelets. The resultant coagulopathy aggravates bleeding from arteriovenous malformations that arise in the mucosal surfaces of the nose and gastrointestinal track.
   • Device-related infections (DLIs) are associated with an increased rate of rehospitalization and mortality. Infection is now recognized as a leading cause of late mortality, usually the result of sepsis, with estimated prevalence of 8% and 18% at 6 and 12 months, respectively, following DLI diagnosis.
   • Stroke: Thromboembolic and hemorrhagic strokes occur with an incidence of 0.19 events per patient-year, but, in general, the former is more common and the latter is more likely to be disabling or fatal. A number of risk factors increase stroke risk such as atrial fibrillation, female sex, hemolysis, and bloodstream infection. Bleeding that necessitates the temporary cessation of anticoagulation is associated with increased thromboembolic stroke risk, even though the average time interval between these two events in the same patient can be as long as 4 months.
   • Pump thrombosis: More recent INTERMACS analyses have concluded that the thrombosis rate is 10%, from a peak of 12.3% in 2012. No single specific cause has been identified to explain the jump in thrombosis rates from the 4-6% observed in clinical trials. Factors implicated include surgical and medical management decisions intentioned to minimize AEs, particularly bleeding, but which may have resulted in unintended consequences. The recent reduction in rates of pump thrombosis are probably due to the readoption of unfractionated heparin in the early post-implant phase, a targeted INR of 2-3, the avoidance of low pump speeds, and the creation of an adequately deep pump pocket to avoid acute angulation of the inflow cannula. Incorporating these practices may explain the low incidence of early (<3 months) pump thrombosis reported by the PREVENT (Prevention of HeartMate II Pump Thrombosis) investigators. Their reported 2.9% occurrence of confirmed pump thrombosis compares favorably well with a historical average of 8.4%, and was achieved without a concomitant increase in other AEs.
5. In the initial 50-patient experience with HeartMate 3 (a next-generation centrifugal flow pump designed to be more biocompatible and reduce AEs), the investigators reported 92% survival free of the need for device exchange or disabling stroke. The ongoing MOMENTUM 3 trial comparing HeartMate 3 with Heart II uses an adaptive trial design with three separate phases: a safety phase (30 patients); a short-term cohort (294 patients, 6-month endpoint); and a long-term cohort (366 patients, 2-year outcomes). There will be a further 622 patients enrolled, examining a secondary endpoint of pump replacement at 2 years, powered to demonstrate the superiority of HeartMate 3 over HeartMate II. Long-term cohort results and imminent detailed hematologic studies from MOMENTUM 3 should shed more light on biocompatibility.
6. The surgical results have improved substantially over the years, and a recent study of destination therapy patients, not dependent on inotropes, reported an operative mortality of 1% and a median hospital stay of 17 days. Although the basic surgical principles for implantation of all LVADs have remained constant over the last 3 decades, there are some notable modifications in surgical approach over recent years including: a) less invasive techniques for LVAD implantation; b) repair of cardiac defects such as mitral stenosis, moderate to severe aortic regurgitation, and atrial septal defect; c) potential sources of thromboembolism, such as LV aneurysms, left atrial appendages (in patients with atrial fibrillation), and mechanical heart valves are often removed or excluded in patients expected to be on LVAD support for prolonged periods; and d) major proximal coronary lesions are considered for concurrent coronary bypass, as ongoing cardiac ischemia could be a trigger for declining native heart function or arrhythmias.
7. Myocardial recovery: The gaps in basic science, as well as clinical knowledge of LVAD facilitated myocardial recovery, must be investigated by multidisciplinary and multicentered approaches that combine the evaluation of the cellular, structural, functional, and clinical attributes of myocardial recovery.
8. Shared decision making should be facilitated given the nuanced clinical outcomes, and possible AEs. The ROADMAP study findings suggest that these patients who delayed LVAD implant did not “pay a penalty” for delaying their decision making.
9. Frailty: An emerging concept is that of selecting patients for lifelong LVAD therapy at a sufficiently early point in time, before the development of frailty. Whether LVAD therapy is sufficient to reverse the frailty phenotype is also a focus of ongoing clinical investigation. A recent study categorized 99 destination therapy patients into tertiles of frailty on the basis of a deficit index. The 1-year mortality for those who were not frail, intermediate frail, and frail were 16.2%, 21.2%, and 39.9% (p = 0.007), respectively. The patients who were frail also had higher readmission rates and spent less time out of hospital than those who were not frail.
10. Cost-effectiveness: Even though the survival advantage of LVAD therapy is clear, further reductions in AEs as well as improvements in quality of life are needed to meet conventional cost-effectiveness thresholds.

Keywords: Aortic Valve Insufficiency, Arrhythmias, Cardiac, Arteriovenous Malformations, Atrial Fibrillation, Blood Platelets, Central Venous Pressure, Cardiac Surgical Procedures, Cost-Benefit Analysis, Geriatrics, Heart Failure, Heart Septal Defects, Atrial, Heart Transplantation, Heart-Assist Devices, Hemolysis, Heparin, Hypovolemia, Mitral Valve Stenosis, Phenotype, Quality of Life, Respiratory Insufficiency, Risk Factors, Sepsis, Shock, Cardiogenic, Stroke, Thromboembolism, Thrombosis, Ventricular Dysfunction, Right, von Willebrand Factor

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