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Nutritional Supplements and the Heart

Vol 15, Issue 3 (2019)


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Dietary Supplements: Facts and Fallacies

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Recent Clinical Trials Shed New Light on the Cardiovascular Benefits of Omega-3 Fatty Acids

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Cardiovascular Risk of Proton Pump Inhibitors

Advanced Cardiac Imaging for Complex Adult Congenital Heart Diseases

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A Rare Case of Pancreatitis-Induced Thrombosis of the Aorta and Superior Mesenteric Artery

Anomalous Origin of the Right Coronary Artery from the Left Main Coronary Artery in the Setting of Critical Bicuspid Aortic Valve Stenosis

Simultaneous Transfemoral Mitral and Tricuspid Valve in Ring Implantation: First Case Report with Edwards Sapien 3 Valve

Uneventful Follow-Up 2 Years after Endovascular Treatment of a High Flow Iatrogenic Aortocaval Fistula Causing Pulmonary Hypertension and Right Heart Failure

MUSEUM OF HMH MULTIMODALITY IMAGING CENTER See More

Snoopy’s Heart: A Case of Complete Congenital Absence of the Pericardium

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POINTS TO REMEMBER

Herbal Nephropathy

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Rolling the Dice on Red Yeast Rice

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The Kidney in Congenital Cyanotic Heart Disease

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Letter to the Editor in Response to “Cardiac Autonomic Neuropathy in Diabetes Mellitus”

Vol 11, Issue 1 (2015)

Article Full Text

REVIEW ARTICLES

Physiological Impact of Continuous Flow on End-Organ Function: Clinical Implications in the Current ERA of Left Ventricular Assist Devices

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Article Citation:

Arvind Bhimaraj, Cesar Uribe, and Erick E. Suarez. Physiological Impact of Continuous Flow on End-Organ Function: Clinical Implications in the Current ERA of Left Ventricular Assist Devices. Methodist DeBakey Cardiovascular Journal. January 2015, Vol. 11, No. 1, pp. 12-17.

doi: https://doi.org/10.14797/mdcj-11-1-12

Abstract

The clinical era of continuous-flow left ventricular assist devices has debunked many myths about the dire need of a pulse for human existence. While this therapy has been documented to provide a clear survival benefit in end-stage heart failure patients, we are now faced with certain morbidity challenges that as of yet have no easy mechanistic physiological explanation. The effect of physiological changes on end-organ function in patients supported by continuous-flow ventricular assist devices may offer insight into some of these morbidities. We therefore present a review of current evidence documenting the impact of continuous flow on end-organ function.

Keywords
continuous flow , CF , left ventricular assist device , LVAD , continuous-flow physiology , end-organ function

Introduction

Continuous-flow left ventricular assist devices (CF-LVADs) have emerged as a robust therapeutic option for end-stage heart failure. Contrary to past scientific skepticism, survival in patients with CF-LVADs has surpassed expectations, with actuarial 1-year survival reaching 80%.1 Though short- and intermediate-term survival advantage of CF-LVADs has been established, the burden of morbidity and cost of non-lethal complications has become more evident.1 As researchers explore the various reasons for such morbidity, the role of physiological alterations due to a lack of pulse emerges as a possibility. In the following, we present a discussion and review of scientific data available regarding the ability of humans to survive without a pulse.

Evolution of Devices

The first-generation VADs were pulsatile pneumatic pumps ejecting blood at 80 to 100 times per minute. Although studies found adverse physiologic alterations with continuous flow,2 the need for portability and durability led to seminal clinical experiments in calves showing successful adaptations with high flows of 80 to 130 mL/kg/min.3 These early studies were viewed with skepticism as most were conducted in healthy animals. When pumps were implanted in animals with cardiogenic shock, blood flow normalization was inferior in CF compared to pulsatile-flow (PF) in the renal cortex (flow in the renal medulla remained the same), hepatic region, and gastric mucosa, although there was no difference in cerebral flow.4 Intravital microscopy of goat skeletal muscle showed that pulsatility was maintained in capillaries, thereby establishing the need of such physiology at the cellular level.5 While some early studies reported successful mechanical support strategies using LVADs with a combination of counter pulsation techniques after cardiotomy shock,6collaborative work between scientists at the National Aeronautical Society of America and surgeons Michael DeBakey and George P. Noon led to the development and successful clinical utilization of CF pumps with the first human implant,7 thus revolutionizing the field of mechanical circulatory support.

Pulsatility in CF-LVADs

The physiology behind CF-LVADs probably does not induce a true lack of a pulse state. Interaction between the native heart and the VAD as two pumps in parallel versus in a series leads to the presence or absence of a pulse pressure.8 Aortic valve opening in the presence of a CF-LVAD is an imaging surrogate marker of pulsatility, and studies from our institution and others have shown a prevalence of aortic valve opening in up to 69% of patients.9,10 Even with a closed aortic valve, pulsatility seems to be present,11possibly due to a contracting left ventricle that transmits a pulsatile flow change through the pump rotor. Nevertheless, the majority of patients on CF-LVADs have a decrease in pulsatility, and some experience a complete loss of pulse.

Clinical Implications of End-Organ Function in CF-LVAD Patients

Renal Function

Animal studies have shown elevated plasma renin levels with CF-LVAD support without a significant rise in blood pressure, while clinical studies in patients waiting for heart transplant on LVAD support showed a decrease in plasma renin and angiotensin II levels.12This reduction occurred earlier than the reduction of plasma volume or atrial natriuretic peptide, suggesting a direct role of LVAD support. A decrease in renal sympathetic nerve activity has also been documented in LVAD-supported dogs.13 Despite early reports of a high incidence of acute renal failure (28% to 45%),14 clinical data has shown improvement in renal function especially in the short term. Sanders et al. compared CF- and PFVAD patients and found comparable improvements from baseline at 12 weeks. Other small studies have confirmed the same up to 15-month follow-up,15 though the baseline glomerular filtration rate (GFR)—especially in those on PF-VADs—was much better in these studies when compared to the Sanders study. Longer-term follow-up in a recent study has shown a GFR improvement from baseline to 6 months but a significant decline when compared to function at 1 and 3 months.16 While a higher pump speed (typically a marker of lower pulsatility) was associated with GFR improvement, so was a higher pulse index (suggestive of more pulsatility). Analysis of the INTERMACS data for a large cohort of patients on CF-LVADs (79%) showed improvements of baseline GFR from ~61 mLl/min/1.73m2 to ~ 83 at 1 month, with a drop in GFR to ~66 at 1 year; 39% had > 50% improvement of GFR at 1 month, while only 17% were able to sustain to 1 year.17 Interestingly, the cohort with a GFR improvement of > 88% at 1 month had the same mortality as the group with no improvement, and both cohorts did worse than the intermediate improvement group. Patients with a decline in GFR from month 1 to 3 had worse outcomes irrespective of early improvements.

As long-term follow-up and efforts to improve survival and morbidity of these patients continues, it is important to ponder the reasons for late worsening of renal function. Multiple factors such as right ventricular failure18 (leading to renal congestion) and micro emboli could be responsible and may represent overall physiological worsening as evidenced by the increased hospitalizations in this cohort.19Imperfect blood pressure measurement while in a CF state, leading to potential overtreatment with medications, is a possibility that warrants closer attention.9 Lack of renal autoregulation at lower flows and hypoperfusion of the kidneys has also been suggested based on observations that at 1 month post-implant, patients who are not on any antihypertensive medications had lower blood pressure and lower creatinine clearance compared to those on medications.20

Cerebral Function

Cerebral blood flow studies in heart failure patients reveal abnormalities lateralized to the right cerebral hemisphere. Interestingly, similar lateralization of stroke has been reported post-CF-LVAD support but has been attributed to microemboli. Infection was also more prevalent in patients with right-sided strokes,21 raising the possibility of inflammation and dysregulation of blood flow as contributing factors. Moreover, microemboli have been found to be prevalent in transcranial Doppler studies in LVAD patients but have not been associated with neurologic outcomes.22

Neurological complications leading to mortality in VAD patients are the second-leading risk after multiorgan failure.1 Beyond general cardiac surgical risk, a cerebral hyperperfusion syndrome due to CF has been suggested.23 Studies of CF-VAD patients in the acute postoperative state showed no difference in cerebral flow regulation and brain injury serum markers (S-100 and neuron-specific enolase) compared to coronary bypass patients.24,25 Neurocognitive function with P300 auditory evoked potentials also was no different in CF physiology.26 In ambulatory CF-LVAD patients, cerebral blood flow has been shown to be 80% of normal controls with no increase on exercise, but increased pump speed augmented cerebral perfusion during exercise.27 In the long-term, normal autoregulatory mechanisms prevail as evidenced by similar autoregulatory index and transfer function gain in CF-LVAD patients compared to those on pulsatile pumps and normal controls.28 None of these physiological changes seem to impact the overall neurocognitive performance in CF-LVAD patients.

Neurological factors are the leading cause of mortality beyond 3 months, with a constant risk up to 48 months.1 Though autopsy studies did not show significant histological changes in the brain arterial circulation in CF-LVAD patients compared to PF patients,29functional alterations cannot be ruled out. Women have a higher incidence of neurological complications,30 raising the possibility of a hormonal impact on arterial biology in the presence of CF. While non-VAD-related factors such as atrial fibrillation, PFO, diabetes, hypercholesterolemia, and smoking contribute to ischemic strokes, factors related to VAD are less clear. Interruption of anticoagulant and antiplatelet medications were responsible for a 47% occurrence of ischemic stroke in the cohort that had a hemorrhagic stroke,30but such interruption was not a contributor for primary ischemic stroke in multivariate analysis. Other possible contributing factors for stroke in CF-LVAD include anatomical factors of outflow graft orientation31 and stasis in the carotid bulb due to increased laminar flow.32 Infection leading to bacteremia and septic emboli are added mechanisms specific to VAD patients due to their high prevalence of chronic infections.33 Bacteremia is associated with a > 8-fold increase in risk of stroke.34 Inflammatory activation and lack of pulsatility impacting endothelial function in the cerebral circulation could have a significant role but has not been studied. The role of blood pressure in neurological adverse events is complicated. Though high blood pressure is thought to perpetuate afterload for the pump and has been suggested to contribute to neurological events, recent data from an aggressive blood pressure control protocol using home Doppler blood pressure measurements showed that patients not on any antihypertensive medications had a higher incidence of neurological adverse events compared to those on medications.20 In fact, despite the fact that the blood pressure was higher in the group on ≥ 2 medications compared to the other groups, there was no increase in neurologic events. Such findings suggest a role of hypoperfusion in cerebral accidents in CF-LVAD patients.

Hemorrhagic stroke occurs in 8% of the patients in the HeartMate-II trials with no difference between the destination and bridge-to-transplant groups.30 Though a high international normalized ratio (INR) could be a simple explanation, many patients have cerebral bleeds in the setting of normal or low INR. Hemorrhagic conversion of an ischemic stroke could be more common in CF-LVAD patients due to their need for anticoagulation. In a single-center study, 47% of the intracranial bleeds were spontaneous intraparenchymal bleeds.35 While association between bleeds and cerebral aneurysms has been suggested, many hemorrhagic strokes are accompanied by negative imaging for an aneurysm. In fact, bleeds in CF-LVAD patients seem to occur in a lobar fashion, similar to amyloid angiopathy and not in deep locations. It is possible that distal capillary networks are impacted by factors such as ongoing inflammation and endothelial cell changes related to a lack of pulsatility. Also, studies have suggested that pathogen-specific factors may contribute to the Pseudomonas bacterium’s predilection for causing hemorrhagic strokes in CF-LVAD patients,36 raising a possibility of antigen vascular interactions in the setting of CF physiology.

Small studies have analyzed other cranial vascular beds. A comparative study of retinal circulation showed no significant morphological changes other than a nonsignificant increase in moderate fluorescein dye leak in the peripapillary areas of CF patients (possibly suggestive of endothelial leak).37 Nasal mucosa in a majority of unselected HeartMate II patients reveled asymptomatic vascular abnormalities.38 Whether such changes are related to lack of pulsatility has not been explored. Nasal bleeding is common, but visual changes have not been reported as a relevant clinical problem.

Myocardial Function

Blood-flow studies using a Jarvik pump in a calf showed that increasing speeds decreased subendo- and epicardial flow,39 although the ratio of blood flow between these two regions remained same. In a small retrospective study in our institution,40 we reviewed a list of genes identified from the literature as endothelial-specific mechanosensitive genes and compared pre and post changes in CF- and PF-VADs. Distinct changes were noticed in CF physiology (Figure 1). For example, eNOS (NOS-3) expression increased more than 200 times after a CF-LVAD implant but decreased after a PF-VAD implant. Contrary to our finding, other studies of PF-VADs found increased eNOS, decreased iNOS, and increased DDAH1 after LVAD support, suggesting improvement of nitric oxide availability.41

Figure 1. Comparison of gene expression analysis in myocardial samples from patients on continuous-flow and pulsatile ventricular assist devices.

Endothelial Function

The endothelium in some perspective is the largest organ that is constantly exposed to the physical forces of normal pulsatility and, along with the vascular smooth muscle cells, perceives these stimuli via special receptors that translate mechanical forces into intracellular metabolic commands.42–44 Such physical forces are also necessary to maintain endothelial integrity. Apart from a longitudinal shear force, cyclic strain as a reflection of pulsatility is an independent modulator of endothelial function45 with a significant impact on NOS3 expression, cell pH, and physical cell alignment at a distinct amount of pulse pressure.46 In an in-vitro perfusion system using segments of human umbilical veins, researchers noted a distinct regulatory impact on various genes by shear and pressure response.47 A total of 1,825 genes (17% of vascular endothelial genes) were found to be either up- or down-regulated by pressure (647 up-regulated; 519 down-regulated), shear stimulation (133 up-regulated; 771 down-regulated), or both. Such data suggests that loss of a pulse pressure could significantly impact endothelial cell function.

While one autopsy study found no histological changes in various vascular beds between CF- and PF-VAD patients,48 another revealed an increase in medial degeneration, smooth muscle cell depletion, elastic fiber fragmentation, and medial fibrosis in the aorta in CF-VAD patients.49 Clinical studies are limited but suggestive of worsening endothelial function with CF-LVADs utilizing flow-mediated vasodilation50 and reactive hyperemia index.16 In some studies, endothelial cell-derived microparticles—small cell vesicles shed during cell activation and apoptosis—were documented in the peripheral blood, suggesting inflammation and cell damage.51 The influence of such changes on clinical outcomes is unknown but hypothetically could be the missing link for mechanistic explanation of many vascular complications.

Hematologic Function

Pump rheological factors impact blood components. Most mechanistic studies involving acquired von Willebrand disease (AvWD) in LVAD patients, which occurs from the loss of high molecular weight fractions, have focused on the impact of shear stress.52 Though shear forces are higher in CF-LVADs compared to pulsatile devices, the significant differences in how these two pumps impact von Willebrand Factor (vWF) and the fact that endothelial cells secrete vWF both suggest that the lack of pulsatility could be partly responsible for AvWD. Also, a recent study by Meyers et al. compared low-shear centrifugal devices and axial flow devices and found no difference in the impact on vWF, suggesting mechanisms beyond shear.53 While shear forces create changes in platelet function and erythrocyte lysis, they likely have no specific link to the lack of pulse pressure. Most studies with CF pumps have shown platelet activation, but a recent study in patients with HeartMate II devices showed no changes in platelet function (measured by soluble P-selectin and CD40L) irrespective of duration of support.54 In a recent, small, single-center study, the interaction between shear forces and blood biomaterial seemed to impact white blood cell immune activation and destruction, leading to phosphatidylserine-positive microparticles that appeared to be associated with adverse clinical outcomes.55 However, any specific association of CF is lacking. There are no studies on the impact of CF-LVADs on bone marrow function.

Gastrointestinal Function

Figure 2. Summary of clinical observations in end-organ function and possible mechanisms related to continuous-flow physiology.

A study by Tuzun et al. showed that blood flow to the abdominal organs (other than renal) had no significant hypo- or hyperperfusion with CF devices in healthy animals.39 In humans, improvement of liver function post-implant is similar to renal function recovery but with sustained long-term improvement. Transaminases are shown to improve consistently by 1 month while bilirubin peaks at day 7 and normalizes by the second month.56 An early increase in bilirubin but not transaminases was suggestive of mortality at 180 days.56Studies comparing changes between CF- and PF-VADs have not found a significant difference in such improvements.15

The mechanism of formation of arteriovenous (AV) malformations in the gut is detailed elsewhere, but the role of pulsatility loss and possibly local endothelial factors such as VEGF and vWF in the formation of vascular malformations is not well established. In a single-center study, we did not find any association between the extent of aortic valve opening (as a surrogate marker of pulse pressure) and clinically significant gastrointestinal AV malformations.10

Other Systems

Reversal of metabolic derangements such as thyroid and skeletal muscle metabolism after LVAD implant has been documented, but there is a limited body of work specific to CF-VADs. While histologic changes in the arteries have been reported in some autopsy studies, the clinical impact of such change in the periphery is not clear. One recent study suggested decreased limb perfusion and adverse outcomes post-LVAD implant.57Figure 2 summarizes clinical observations in end-organ function and possible mechanisms related to continuous-flow physiology.

Conclusion

Continuous-flow left ventricular assist devices have allowed humans to defy nature by enduring extreme changes in physiology. With the concept of total implantable continuous-flow pumps, artificial pulse technology, and transcutaneous energy transfer, continuous-flow physiology is here to stay. At this point many of the end-organ function-change studies have been observational, with some mechanistic postulations (Figure 2), and need further research to better understand the impact of such physiology on the human body.

Conflict of Interest Disclosure

The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

Funding/Support: The authors have nothing to disclose.

References
1. Kirklin JK , Naftel DC , Pagani FD et al. Sixth INTERMACS annual report: a 10,000-patient databaseJ Heart Lung Transplant2014 Jun;33(6):55564[Crossref]
2. Taylor KM , Wright GS , Bain WH , Caves PK , Beastall GS. Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. III. Response of anterior pituitary gland to thyrotropin-releasing hormoneJ Thorac Cardiovasc Surg1978 Apr;75(4):57984.
3. Yada I , Golding LR , Harasaki H et al. Physiopathological studies of nonpulsatile blood flow in chronic modelsTrans Am Soc Artif Intern Organs1983;29:5205.
4. Orime Y , Shiono M , Nakata K et al. The role of pulsatility in endorgan microcirculation after cardiogenic shockASAIO J1996 Sep–Oct;42(5):M7249[Crossref]
5. Lee JJ , Tyml K , Menkis AH , Novick RJ , McKenzie FN. Evaluation of pulsatile and nonpulsatile flow in capillaries of goat skeletal muscle using intravital microscopyMicrovasc Res1994 Nov;48(3):31627[Crossref]
6. Golding LR , Jacobs G , Groves LK , Gill CC , Nosé Y , Loop FD. Clinical results of mechanical support of the failing left ventricleJ Thorac Cardiovasc Surg1982 Apr;83(4):597601.
7. Wieselthaler GM , Schima H , Hiesmayr M et al. First clinical experience with the DeBakey VAD continuous-axial-flow pump for bridge to transplantationCirculation2000 Feb;101(4):3569[Crossref]
8. Travis AR , Giridharan GA , Pantalos GM et al. Vascular pulsatility in patients with a pulsatile- or continuous-flow ventricular assist deviceJ Thorac Cardiovasc Surg2007 Feb;133(2):51724[Crossref]
9. Bhimaraj A , Bellera RV , Martinez D et al. Interaction of pulse perception, blood pressure measurements (by Doppler and standard cuff techniques) and visual assessment of aortic valve opening in continuous flow LVAD patients in the outpatient settingJ Heart Lung Transplant2014 Apr;33(4):S134[Crossref]
10. Bhimaraj A , Hall D , Vivo R et al. 561 Maintaining pulsatility or not with intermittent aortic valve opening does not appear to contribute to formation of AV malformation in patients with continuous-flow left ventricular assist devicesJ Heart Lung Transplant2012 Apr;31(4):S195[Crossref]
11. Melisurgo G , De Bonis M , Pieri M et al. Is flow really continuous in last generation continuous flow Ventricular Assist Devices? A comparison between HeartMate II and HeartWare HVADHSR Proc Intensive Care Cardiovasc Anesth2012;4(4):2689.
12. James KB , McCarthy PM , Thomas JD et al. Effect of the implantable left ventricular assist device on neuroendocrine activation in heart failureCirculation1995 Nov 1;92(9 Suppl):II1915[Crossref]
13. Mao H , Katz N , Kim JC , Day S , Ronco C. Implantable left ventricular assist devices and the kidneyBlood Purif2014;37(1):5766[Crossref]
14. Borgi J , Tsiouris A , Hodari A , Cogan CM , Paone G , Morgan JA. Significance of postoperative acute renal failure after continuousflow left ventricular assist device implantationAnn Thorac Surg2013 Jan;95(1):1639[Crossref]
15. Radovancevic B , Vrtovec B , de Kort E , Radovancevic R , Gregoric ID , Frazier OH. End-organ function in patients on longterm circulatory support with continuous- or pulsatile-flow assist devicesJ Heart Lung Transplant2007 Aug;26(8):8158[Crossref]
16. Hasin T , Topilsky Y , Schirger JA et al. Changes in renal function after implantation of continuous-flow left ventricular assist devicesJ Am Coll Cardiol2012 Jan;59(1):2636[Crossref]
17. Brisco MA , Kimmel SE , Coca SG et al. Prevalence and prognostic importance of changes in renal function after mechanical circulatory supportCirc Heart Fail2014 Jan;7(1):6875[Crossref]
18. Saxena S , Um J , Dumitru I et al. Improvement in severe kidney dysfunction after implantation of continuous-flow left ventricular assist devicesJ Heart Lung Transplant2013 Apr;32(4):S275[Crossref]
19. John A , Ghotra A , Sinha R , Lenneman A , Birks E , McCants K. Trends in glomerular filtration rate (GFR) following implantation of continuous flow left ventricular assist devices (LVAD)J Card Fail2014 Aug;20(8S):S90[Crossref]
20. Lampert BC , Eckert C , Weaver S et al. Blood pressure control in continuous flow left ventricular assist devices: efficacy and impact on adverse eventsAnn Thorac Surg2014 Jan;97(1):13946[Crossref]
21. Kato TS , Ota T , Schulze PC et al. Asymmetric pattern of cerebrovascular lesions in patients after left ventricular assist device implantationStroke2012 Mar;43(3):8724[Crossref]
22. Garami Z , Livia K , Brian B et al. 768 Transcranial Doppler findings in heart failure patients with left ventricular assist devices (LVADs)J Heart Lung Transplant2012 Apr;31(4):S262[Crossref]
23. Lietz K , Brown K , Ali SS et al. The role of cerebral hyperperfusion in postoperative neurologic dysfunction after left ventricular assist device implantation for end-stage heart failureJ Thorac Cardiovasc Surg2009 Apr;137(4):10129[Crossref]
24. Ono M , Joshi B , Brady K et al. Cerebral blood flow autoregulation is preserved after continuous-flow left ventricular assist device implantationJ Cardiothorac Vasc Anesth2012 Dec;26(6):10228[Crossref]
25. Potapov EV , Loebe M , Abdul-Khaliq H et al. Postoperative course of S-100B protein and neuron-specific enolase in patients after implantation of continuous and pulsatile flow LVADsJ Heart Lung Transplant2001 Dec;20(12):13106[Crossref]
26. Zimpfer D , Wieselthaler G , Czerny M et al. Neurocognitive function in patients with ventricular assist devices: a comparison of pulsatile and continuous blood flow devicesASAIO J2006 Jan–Feb;52(1):247[Crossref]
27. Brassard P , Jensen AS , Nordsborg N et al. Central and peripheral blood flow during exercise with a continuous-flow left ventricular assist device: constant versus increasing pump speed: a pilot studyCirc Heart Fail2011 Sep;4(5):55460[Crossref]
28. Cornwell WK , Tarumi T , Aengevaeren V et al. Effect of pulsatile and nonpulsatile flow on cerebral perfusion in patients with LVADsJ Heart Lung Transplant2014 Apr;33(4):S144[Crossref]
29. Potapov EV , Dranishnikov N , Morawietz L et al. Arterial wall histology in chronic pulsatile-flow and continuous-flow device circulatory supportJ Heart Lung Transplant2012 Nov;31(11):11716[Crossref]
30. Boyle AJ , Jorde UP , Sun B et al. Pre-operative risk factors of bleeding and stroke during left ventricular assist device support: an analysis of more than 900 HeartMate II outpatientsJ Am Coll Cardiol2014 Mar 11;63(9):8808[Crossref]
31. Osorio AF , Osorio R , Ceballos A et al. Computational fluid dynamics analysis of surgical adjustment of left ventricular assist device implantation to minimise stroke riskComput Methods Biomech Biomed Engin2013;16(6):62238[Crossref]
32. Reul JT , Reul GJ , Frazier OH. Carotid-bulb thrombus and continuous-flow left ventricular assist devices: a novel observationJ Heart Lung Transplant2014 Jan;33(1):1079[Crossref]
33. Kato TS , Schulze PC , Yang J et al. Pre-operative and post-operative risk factors associated with neurologic complications in patients with advanced heart failure supported by a left ventricular assist deviceJ Heart Lung Transplant2012 Jan;31(1):18.[Crossref]
34. Aggarwal A , Gupta A , Kumar S et al. Are blood stream infections associated with an increased risk of hemorrhagic stroke in patients with a left ventricular assist device? ASAIO J. 2012 Sep–Oct;58(5):50913[Crossref]
35. Wilson TJ , Stetler WR Jr , Al-Holou WN , Sullivan SE , Fletcher JJ. Management of intracranial hemorrhage in patients with left ventricular assist devicesJ Neurosurg2013 May;118(5):10638[Crossref]
36. Trachtenberg BH , Aldeiri M , Cordero-Reyes AM et al. Persistent blood stream infections are associated with cerebrovascular accidents in patients with continuous flow LVADsJ Heart Lung Transplant2014 Apr;33(4):S212[Crossref]
37. Ozturk T , Nalcaci S , Ozturk P et al. Fundus fluorescein angiographic findings in patients who underwent ventricular assist device implantationArtif Organs2013 Sep;37(9):81620.
38. Fida N , Maybaum S , Jackman AJ et al. Abstract 16781: Nasal microvasculature changes during continuous flow left ventricular assist device (CF-LVAD) supportCirculation2013;128:A16781.
39. Tuzun E , Chorpenning K , Liu MQ et al. The effects of continuous and intermittent reduced speed modes on renal and intestinal perfusion in an ovine modelASAIO J2014 Jan–Feb;60(1):1924[Crossref]
40. Bhimaraj A , Uribe C , Youker KA et al. Endothelial cells have a distinct response to continuous flow pump support compared to pulsatile flow pump support. A gene expression analysis study of paired myocardial samplesJ Card Fail2014 Aug;20(8):S26.[Crossref]
41. Chen Y , Park S , Li Y et al. Alterations of gene expression in failing myocardium following left ventricular assist device supportPhysiol Genomics2003 Aug 15;14(3):25160[Crossref]
42. Liedtke W. TRPV channels’ role in osmotransduction and mechanotransductionHandb Exp Pharmacol2007;(179):47387.[Crossref]
43. Ohno M , Gibbons GH , Dzau VJ , Cooke JP. Shear stress elevates endothelial cGMP. Role of a potassium channel and G protein couplingCirculation1993 Jul;88(1):1937[Crossref]
44. Ohno M , Cooke JP , Dzau VJ , Gibbons GH. Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium channel blockadeJ Clin Invest1995 Mar;95(3):13639[Crossref]
45. Thubrikar MJ Robicsek F. Pressure-induced arterial wall stress and atherosclerosisAnn Thorac Surg1995 Jun;59(6):1594603.[Crossref]
46. Peng X , Recchia FA , Byrne BJ , Wittstein IS , Ziegelstein RC , Kass DA. In vitro system to study realistic pulsatile flow and stretch signaling in cultured vascular cellsAm J Physiol Cell Physiol2000 Sep;279(3):C797805.
47. Andersson M , Karlsson L , Svensson PA et al. Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressureJ Vasc Res2005 Sep–Oct;42(5):44152[Crossref]
48. Potapov EV , Dranishnikov N , Morawietz L et al. Arterial wall histology in chronic pulsatile-flow and continuous-flow device circulatory supportJ Heart Lung Transplant2012 Nov;31(11):11716[Crossref]
49. Segura AM , Gregoric I , Radovancevic R , Demirozu ZT , Buja LM , Frazier OH. Morphologic changes in the aortic wall media after support with a continuous-flow left ventricular assist deviceJ Heart Lung Transplant2013 Nov;32(11):1096100[Crossref]
50. Amir O , Radovancevic B , Delgado RM 3rd , et al. Peripheral vascular reactivity in patients with pulsatile vs axial flow left ventricular assist device supportJ Heart Lung Transplant2006 Apr;25(4):3914[Crossref]
51. Diehl P , Aleker M , Helbing T et al. Enhanced microparticles in ventricular assist device patients predict platelet, leukocyte and endothelial cell activationInteract Cardiovasc Thorac Surg2010 Aug;11(12):1337[Crossref]
52. Baldauf C , Schneppenheim R , Stacklies W et al. Shearinduced unfolding activates von Willebrand factor A2 domain for proteolysisJ Thromb Haemost2009 Dec;7(12):2096105[Crossref]
53. Meyer AL , Malehsa D , Budde U , Bara C , Haverich A , Strueber M. Acquired von Willebrand syndrome in patients with a centrifugal or axial continuous flow left ventricular assist deviceJACC Heart Fail2014 Apr;2(2):1415[Crossref]
54. Slaughter MS , Sobieski MA 2nd , Graham JD , Pappas PS , Tatooles AJ , Koenig SC. Platelet activation in heart failure patients supported by the HeartMate II ventricular assist deviceInt J Artif Organs2011 Jun;34(6):4618[Crossref]
55. Nascimbene A , Hernandez R , George JK et al. Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devicesJ Heart Lung Transplant2014 May;33(5):4707[Crossref]
56. Russell SD , Rogers JG , Milano CA et al. Renal and hepatic function improve in advanced heart failure patients during continuous-flow support with the HeartMate II left ventricular assist deviceCirculation2009 Dec 8;120(23):23527[Crossref]
57. Ohman JW , Vemuri C , Prasad S , Silvestry SC , Jim J , Geraghty PJ. The effect of extremity vascular complications on the outcomes of cardiac support device recipientsJ Vasc Surg2014 Jun;59(6):16227[Crossref]

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