"Neurologic Complications in Patients with Left Ventricular Assist Devices".

Reduced arterial pulsatility in continuous-flow left ventricular assist devices (CF-LVAD) patients has been implicated in clinical complications. Consequently, recent improvements in clinical outcomes have been attributed to the "artificial pulse" technology inherent to the HeartMate3 (HM3) LVAD. However, the effect of the "artificial pulse" on arterial flow, transmission of pulsatility into the microcirculation and its association with LVAD pump parameters is not known.The local flow oscillation (pulsatility index, PI) of common carotid arteries (CCAs), middle cerebral arteries (MCAs) and central retinal arteries (CRAs-representing the microcirculation) were quantified by 2D-aligned, angle-corrected Doppler ultrasound in 148 participants: healthy controls, n = 32; heart failure (HF), n = 43; HeartMate II (HMII), n = 32; HM3, n = 41.In HM3 patients, 2D-Doppler PI in beats with "artificial pulse" and beats with "continuous-flow" was similar to that of HMII patients across the macro- and microcirculation. Additionally, peak systolic velocity did not differ between HM3 and HMII patients. Transmission of PI into the microcirculation was higher in both HM3 (during the beats with "artificial pulse") and in HMII patients compared with HF patients. LVAD pump speed was inversely associated with microvascular PI in HMII and HM3 (HMII, r2 = 0.51, p < 0.0001; HM3 "continuous-flow," r2 = 0.32, p = 0.0009; HM3 "artificial pulse," r2 = 0.23, p = 0.007), while LVAD pump PI was only associated with microcirculatory PI in HMII patients.The "artificial pulse" of the HM3 is detectable in the macro- and microcirculation but without creating a significant alteration in PI compared with HMII patients. Increased transmission of pulsatility and the association between pump speed and PI in the microcirculation indicate that the future clinical care of HM3 patients may involve individualized pump settings according to the microcirculatory PI in specific end-organs. 

Pulsatility and Flow Patterns across Macro- and Microcirculatory Arteries of Continuous-Flow Left Ventricular Assist Device Patients.

HomeCirculation: Heart FailureVol. 16, No. 11HeartMate 3 Left Ventricular Assist Device Improves Long-Term Cerebral Hemodynamics Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBHeartMate 3 Left Ventricular Assist Device Improves Long-Term Cerebral Hemodynamics Christopher G. Favilla, Sarah Carter, Pavan Atluri, Navpreet Reehal and Michael V. Genuardi Christopher G. FavillaChristopher G. Favilla Correspondence to: Christopher G. Favilla, MD, University of Pennsylvania, 3400 Spruce St, 3 W Gates Bldg, Philadelphia, PA 19104. Email E-mail Address: [email protected] https://orcid.org/0000-0003-0871-9549 Department of Neurology (C.G.F., S.C., N.R.), University of Pennsylvania, Philadelphia. Search for more papers by this author , Sarah CarterSarah Carter Department of Neurology (C.G.F., S.C., N.R.), University of Pennsylvania, Philadelphia. Search for more papers by this author , Pavan AtluriPavan Atluri https://orcid.org/0000-0003-0229-085X Department of Cardiothoracic Surgery (P.A.), University of Pennsylvania, Philadelphia. Search for more papers by this author , Navpreet ReehalNavpreet Reehal Department of Neurology (C.G.F., S.C., N.R.), University of Pennsylvania, Philadelphia. Search for more papers by this author and Michael V. GenuardiMichael V. Genuardi https://orcid.org/0000-0002-8008-7526 Department of Medicine, Division of Cardiology (M.V.G.), University of Pennsylvania, Philadelphia. Search for more papers by this author Originally published6 Nov 2023https://doi.org/10.1161/CIRCHEARTFAILURE.123.010675Circulation: Heart Failure. 2023;16Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: November 6, 2023: Ahead of Print The left ventricular assist device (LVAD) has revolutionized clinical management of advanced heart failure.1 Although the overarching goal is to offload the heart and improve vital organ perfusion, the impact of LVAD implantation on cerebral hemodynamics, particularly in the long term, remains poorly understood. Cerebral hemodynamic impairment is a key contributor to stroke and cognitive decline, both of which are critical considerations in an ever growing and aging LVAD population.2 Here, we aimed to serially monitor cerebral blood flow velocity (CBFv) with transcranial Doppler before and after LVAD implantation, leveraging these data to quantify 2 dynamic measures of cerebrovascular health: cerebral autoregulation (CA) and cerebrovascular reactivity (CVR). CA describes the relationship between blood pressure (BP) and cerebral blood flow, while CVR quantifies hemodynamic reserve.3 Both CA and CVR are impaired in advanced heart failure, but it is unclear to what degree LVAD implantation improves these metrics.2 We hypothesize that LVAD implantation improves CA and CVR. Characterizing these parameters may be crucial to understanding neurological outcomes in patients with LVAD, with the eventual goal of titrating LVAD parameters to optimize cerebral physiology.This single-center cohort included patients ≥18 years of age with advanced heart failure, scheduled to undergo HeartMate 3 (Abbott Laboratories, Chicago, IL) LVAD implantation between November 2020 and March 2022. This study was approved by the University of Pennsylvania Institutional Review Board. Patients provided written informed consent before study participation. The data that support the reported findings are available from the corresponding author upon reasonable request.The protocol included 4 study visits: (1) <72 hours pre-implant, (2) <72 hours post-implant, (3) 14 days post-implant, and (4) 90 days post-implant. During each study visit, BP was continuously monitored by finger plethysmography (Finapres NOVA; Finapres Medical Systems, Enschede, the Netherlands) on the patients’ wrist and third digit. The left middle cerebral artery CBFv was monitored by a RobotoC9MD Neurovision transcranial Doppler (Multigon Industries Inc, Elmsford, NY). CBFv and BP waveforms were synchronized and recorded at 125 Hz. CA was quantified by the Mx index, which represents the correlation of CBFv and BP during 10 minutes of monitoring at rest (ie, higher Mx index indicates impaired CA). CVR, or hemodynamic reserve, was assessed by quantifying the change in CBFv induced by a hypercapnic stimulus (5% inhaled CO2). CVR was not assessed immediately post-implant, citing safety:CVR=CBFvhypercapnia−CBFvnormocapniaCBFvnormocapnia×100ΔCO2Hemodynamic parameters were compared across all study visits using Kruskal-Wallis tests. Wilcoxon signed-rank tests compared each postimplant parameter with baseline.Each of the 20 patients enrolled completed at least 2 study visits, but 15 completed the protocol in its entirety−3 expired, 1 withdrew, and 1 remained hospitalized >90 days and was hemodynamically unstable at study visit 4. Patients had a mean age of 65 years (±9), and 20% were women.BP was similar across all study sessions (P=0.61), and preimplant BP was similar to each postimplant visit (Figure [A]). CBFv was similar across all study visits (P=0.69), and preimplant CBFv was similar to each postimplant visit (Figure [B]). Differences were noted in the more dynamic cerebrovascular parameters. CA varied across the 4 study visits (P=0.004); as compared with baseline CA, improvement was observed at each postimplant evaluation (Figure [C]). CVR also varied across the study visits (P=0.04); as compared with the baseline CVR, improvement was noted at 90 days. The CVR point estimate at 14 days raises the possibility of improvement, but this was nonsignificant (Figure [D]).Download figureDownload PowerPointFigure. Cerebral hemodynamics before and after left ventricular assist device implantation. A, Mean arterial pressure was assessed by finger plethysmography during each study visit. Pairwise comparisons were performed using Wilcoxon signed-rank tests. B, Cerebral blood flow velocity was monitored in the middle cerebral artery trunk during each study visit. Pairwise comparisons were performed using Wilcoxon signed-rank tests. C, Cerebral autoregulation was quantified as the Mx index during each of the 4 study visits. Lower Mx index indicates more favorable autoregulation. Pairwise comparisons were performed using Wilcoxon signed-rank tests. D, Cerebrovascular reactivity was calculated during 3 study visits. Pairwise comparisons were performed using Wilcoxon signed-rank tests.This is the first longitudinal assessment of CA and CVR after LVAD implantation. We observed improvements in dynamic cerebrovascular measures of autoregulation and vascular reactivity after LVAD implant, without a change in CBFv. With respect to CA, we observed both an immediate and sustained improvement, but statistical significance does not necessarily convey a clinically meaningful difference, which requires correlation with clinically meaningful end points. In contrast, a prior study noted no change in CA immediately post-implant.4 The improvement observed here may suggest a brief temporal delay in CA restoration. More extensive postimplant monitoring may clarify the precise timing of CA restoration. Although we observed no change in CVR after 14 days, the 90-day improvement reflects the availability of additional hemodynamic reserve. The time delay in CVR augmentation may indicate long-term cerebrovascular adaptation. On the contrary, the 14-day point estimate raises the possibility of a meaningful improvement in CVR, but the cohort may have been underpowered or limited by heterogeneity at this time point. A prior cross-sectional study found that CVR was similar in HeartMate 3 patients and heart failure patients, both of which were worse than healthy adults.5 With longitudinal pairwise assessment, we are able to more clearly characterize the effect of the HeartMate 3 on CVR.Cerebral hemodynamic impairment is a key contributor to brain health. Although this report does not entirely unravel the complex relationship between LVAD and cerebral hemodynamics, it provides critical insights and justifies future studies that will include longer follow-up and correlate post-LVAD cerebral hemodynamics with clinically meaningful end points such as stroke and cognitive decline.ARTICLE INFORMATIONSources of FundingThis work was supported, in part, by the National Institutes of Health (NIH; K23-NS110993, Dr Favilla), the National Center for Advancing Translational Sciences of the NIH, and the Institute for Translational Medicine and Therapeutics’ Transdisciplinary Program in Translational Medicine and Therapeutics (UL1TR001878, subaward to Drs Favilla and Genuardi).Nonstandard Abbreviations and AcronymsBPblood pressureCAcerebral autoregulationCBFvcerebral blood flow velocityCVRcerebrovascular reactivityLVADleft ventricular assist deviceDisclosures Dr Genuardi reports consulting income from Respicardia and a research agreement with Abbott. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page 995.Correspondence to: Christopher G. Favilla, MD, University of Pennsylvania, 3400 Spruce St, 3 W Gates Bldg, Philadelphia, PA 19104. Email christopher.favilla@pennmedicine.upenn.eduREFERENCES1. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2022; 145:e895–e1032. doi: 10.1161/CIR.0000000000001063LinkGoogle Scholar2. Shoskes A, Fan TH, Starling RC, Cho SM. Neurologic complications in patients with left ventricular assist devices.Can J Cardiol. 2023; 39:210–221. doi: 10.1016/j.cjca.2022.11.004CrossrefMedlineGoogle Scholar3. Purkayastha S, Sorond F. Transcranial Doppler ultrasound: technique and application.Semin Neurol. 2012; 32:411–420. doi: 10.1055/s-0032-1331812CrossrefMedlineGoogle Scholar4. Ono M, Joshi B, Brady K, Easley RB, Kibler K, Conte J, Shah A, Russell SD, Hogue CW. Cerebral blood flow autoregulation is preserved after continuous-flow left ventricular assist device implantation.J Cardiothorac Vasc Anesth. 2012; 26:1022–1028. doi: 10.1053/j.jvca.2012.07.014CrossrefMedlineGoogle Scholar5. Stohr EJ, Ji R, Akiyama K, Mondellini G, Braghieri L, Pinsino A, Cockcroft JR, Yuzefpolskaya M, Amlani A, Topkara VK, et al. Cerebral vasoreactivity in HeartMate 3 patients.J Heart Lung Transplant. 2021; 40:786–793. doi: 10.1016/j.healun.2021.05.005CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 2023Vol 16, Issue 11 Advertisement Article Information Metrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.123.010675PMID: 37929601 Originally publishedNovember 6, 2023 Keywordscerebrovsacular circulationgoalsheart failurehumansperfusionPDF download Advertisement Subjects Cerebrovascular Disease/Stroke Heart Failure Hemodynamics 

HeartMate 3 Left Ventricular Assist Device Improves Long-Term Cerebral Hemodynamics

Current status and future directions in pediatric ventricular assist device.

Article published in Journal of Heart and Lung Transplantation available at https://doi.org/10.1016/j.healun.2021.05.005

Cerebral vasoreactivity in HeartMate 3 patients.

Postdischarge Functional Capacity, Health-Related Quality of Life, Depression, Anxiety, and Post-traumatic Stress Disorder in Patients Receiving a Long-term Left Ventricular Assist Device.

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Cerebral vasoreactivity in HeartMate 3 patients.

Postdischarge Functional Capacity, Health-Related Quality of Life, Depression, Anxiety, and Post-traumatic Stress Disorder in Patients Receiving a Long-term Left Ventricular Assist Device.