Periodic Reporting for period 2 - HIT-LVAD (Understanding blood pressure and vascular haemodynamics in implanted Left Ventricular Assist Device patients.)
Reporting period: 2018-09-01 to 2019-08-31
"Although the remarkable improvements in medical progress are considered a positive achievement, they also create new societal challenges. For example, more people survive events such as heart attacks, thereby increasing the number of older people at risk of developing “heart failure” (HF). Indeed, ~15 Mio people are at risk of HF in Europe, of which 600 000 – 750 000 require “advanced cardiac care” and ultimately a heart transplant. Since not enough donor hearts are available, the second-best option is the surgical implantation of a mechanical heart pump, a so-called left ventricular assist device (LVAD).
Historically, the second-generation LVAD patients (2G-LVAD pts) have significantly improved the survival of patients with advance HF, despite producing continuous flow and ""humans with no pulse"". Unfortunately, patients can still develop serious complications such as gastrointestinal bleeding, right heart failure, and stroke, categorised as “haemodynamic issues”. For this reason, the HIT-LVAD project was initiated, with the overall aim to improve the current understanding of the physiology that underpins the drastically altered circulation in 2G-LVAD pts, thus assisting in explaining risk in those on non-pulsatile LVADs."
Historically, the second-generation LVAD patients (2G-LVAD pts) have significantly improved the survival of patients with advance HF, despite producing continuous flow and ""humans with no pulse"". Unfortunately, patients can still develop serious complications such as gastrointestinal bleeding, right heart failure, and stroke, categorised as “haemodynamic issues”. For this reason, the HIT-LVAD project was initiated, with the overall aim to improve the current understanding of the physiology that underpins the drastically altered circulation in 2G-LVAD pts, thus assisting in explaining risk in those on non-pulsatile LVADs."
To date, the action has successfully completed most of its aims and generated 35 research items (articles, 1 video, 1 podcast, abstracts, posters). The Marie Skłodowska-Curie Fellow has also successfully trained a successor, thereby ensuring the continuation of the HIT-LVAD project and a more permanent collaboration with Columbia University beyond the 36 months of the action. In summary, the HIT-LVAD project has made contact with ~250 LVAD patients; presented data at 15 conferences (including 4 symposia), and fostered relationships with three industrial partners.
Specifically, the action has created the largest database of haemodynamics in LVAD, showing that heart failure patients have an increased pulsatility, while 2G-LVAD pts have a substantially increased flow in the microcirculation. Together with the successful completion of a study revealing the impact of blood pressure on risk in 2G-LVAD pts, and the simultaneous validation of a blood pressure monitor, clinicians can now assess blood pressure in these patients and manage the disease in a better manner, thus reducing complications and improving the patients’ lives. Similarly, the HIT-LVAD peoject showed that aortic stiffness is related to clinical outcomes in 2G-LVAD pts, and that carotid artery plaques present prior to LVAD surgery are likely ot play a previously underestimated role in complications in LVAD pts. in addition to the original aims of the action, the research has been extended to 3G-LVAD, refuting the current belief that 3G-LVAD pts have an increased pulsatility. This highly highly novel, timely and clinically-relevant advancement to the current thinking creates the opportunity for a large body of research into the specific mechanisms of improved outcomes in 3G-LVAD pts. Finally, the action has been able to show that 3G-LVAD pts have an improved reactivity in their brains, and current efforts into validating a blood pressure monitor in this cohort will further advance the knowledge and socio-economic impact of the HIT-LVAD project.
Specifically, the action has created the largest database of haemodynamics in LVAD, showing that heart failure patients have an increased pulsatility, while 2G-LVAD pts have a substantially increased flow in the microcirculation. Together with the successful completion of a study revealing the impact of blood pressure on risk in 2G-LVAD pts, and the simultaneous validation of a blood pressure monitor, clinicians can now assess blood pressure in these patients and manage the disease in a better manner, thus reducing complications and improving the patients’ lives. Similarly, the HIT-LVAD peoject showed that aortic stiffness is related to clinical outcomes in 2G-LVAD pts, and that carotid artery plaques present prior to LVAD surgery are likely ot play a previously underestimated role in complications in LVAD pts. in addition to the original aims of the action, the research has been extended to 3G-LVAD, refuting the current belief that 3G-LVAD pts have an increased pulsatility. This highly highly novel, timely and clinically-relevant advancement to the current thinking creates the opportunity for a large body of research into the specific mechanisms of improved outcomes in 3G-LVAD pts. Finally, the action has been able to show that 3G-LVAD pts have an improved reactivity in their brains, and current efforts into validating a blood pressure monitor in this cohort will further advance the knowledge and socio-economic impact of the HIT-LVAD project.
As outlined above, the HIT-LVAD project has already generated a variety of different outputs, some which are final and many more that are preliminary, as indicated by abstracts, posters and presentations. Furthermore, the opportunity to compare the biology of the 3GLVAD with other LVADs as well as with the physiology of healthy controls presents a unique opportunity that is expected to generate high-impact publications in leading medical journals. One reason why the HIT-LVAD project can be reasonably expected to produce such high-profile publications with wide-reaching impact is the current lack of knowledge and the reliance on assumptions amongst medics. For example, because of an in-built ‘artificial pulse’,1 the 3rd generation LVAD is expected by practitioners to ‘add pulsatility’ to the circulation of these patients. However, the HIT-LVAD project has collected unique data that contradict this currently wide-held belief. Specifically, a prospective study by the HIT-LVAD project reveals that the average pulsatility of the 3GLVAD is no different from that of the 2GLVAD. This finding is of huge importance, as it will impact on the interpretation of the biology of these patients, which may influence the diagnostic approach and the therapeutic management of these patients. As such, the HIT-LVAD project is expected to have a large impact on a wide range of clinical personnel (nurses for education and knowledge of the biology of the patients; clinicians for education and knowledge of the biology of the patients as well as diagnostic and therapeutic decision making; and clinical researchers). In addition, the findings from the HIT-LVAD project are expected to impact on the patients, by either providing the basis to modify existing LVAD parameters/settings based upon the updated knowledge, but also by impacting on the patient’s wellbeing through an enhanced confidence in the knowledge of the underlying biology that is associated with 3GLVADs. Consequently, patients may feel less anxious and will be able to have more precise conversations with their cardiologists and nurses about the progression of their condition. Similarly, the findings are expected to impact engineers who work on developing and improving new medical devices such as LVADs, by providing the scientific knowledge that can be transferred to medicine, research and industry. Because of the findings of the HIT-LVAD project, future LVAD developers are likely to consult the HIT-LVAD team for advice on the optimisation of mechanical heart pumps, as has already happened with a group from France. In this regard, the HIT-LVAD project is also expected to have significant economic impact as the findings lend themselves to the improvement of existing devices (LVADs, BP monitors etc.) as well as the generation of potentially new devices. Should the efforts of amended BP monitors be successful, the HIT-LVAD project would be the first and only in the world to provide an evidence-based BP monitor for these patients. At present, the action concludes that any improvements in risk require more detailed clinical monitoring of LVAD patients that take into account the new blood pressure, micro- and macrocirculatory patterns highlighted by the action.