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Durable continuous-flow left ventricular assist devices (cfLVADs) demonstrate superior survival, cardiac functional status, and overall quality of life compared to medical therapy alone in advanced heart failure. Previous studies have not considered the impact arterial compliance may have on pump performance or developed arterial pressure. This study assessed the impact of alterations in arterial compliance, preload, and afterload on continuous-flow pump function and measured hemodynamics using an in-vitro pulsatile mock circulatory loop. Decreased arterial compliance was associated with a significant increase in arterial pressure pulsatility which was not evident in the flow pulsatility, as displayed in pump flow waveforms. There were marked changes in the pump flow waveforms due to the significant alteration in the aortoventricular gradient during diastole according to the changes in compliance. This study demonstrates that changes in systemic blood pressure, afterload, and left ventricular contractility each significantly affects the flow waveform. The association of hypertension with lower aortic compliance results in markedly decreased diastolic flow rates which may be important in contributing to a greater risk of adverse events under cfLVAD support.

Background: Veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) may cause adverse effects including increased left ventricular (LV) filling pressure, LV distension and pulmonary oedema. We aimed to quantify the effects of ECMO flow, LV contractility, aortic pressure (AoP) and ECMO configuration on left atrial pressure (LAP) during VA-ECMO for cardiogenic shock in a mock circulatory loop (MCL). Methods: An MCL simulated a normal state, LV failure, right ventricular failure and biventricular failure. The ECMO return cannula was placed in the femoral artery (retrograde flow) or ascending aorta (antegrade flow). ECMO flow was incrementally increased from 0 to 5L/min. LAP, mean AoP, ECMO flow and total cardiac output were measured at steady state. Results: During VA-ECMO, LAP increased linearly with AoP, with the slope greater in the presence of LV impairment compared to preserved LV function. When AoP was held constant, as is the goal of therapy in clinical management, ECMO flow had no effect on LAP. In multivariable linear regression, AoP and LV contractility (pConclusion:AoP and LV contractility, but not circuit flow or direction, independently determine LAP under VA-ECMO support. By controlling each of these inputs, vasodilator and inotrope management may combine synergistically to prevent VA-ECMO-related complications.

Background and Aim: The left ventricle (LV) faces a dual afterload in patients with aortic stenosis (AS) – both from the valve and vasculature. Together they form the global LV load. Two cardiac magnetic resonance (CMR) techniques have been described to quantify global LV load: (1) valvulo-arterial impedance instantaneous (ZVA-INS) and (2) valvulo-arterial load (VAL). The purpose of this study was to evaluate concordance (if any) between ZVA-INS and VAL. Methods: Twenty AS patients were compared (80 ± 9 years; 12 males; 80% severe). Aortic flow velocity data was obtained during breath-hold using through-plane PC Qflow imaging. ZVA-INS was determined as the relationship of aortic pressure and maximum aortic valve (AV) gradient to ascending aorta flow velocity in the time domain. VAL was determined as the relationship of aortic pressure to ascending aorta flow velocity in the frequency domain. Values from both methods were compared against total arterial compliance (TAC). Results: Global LV load was significantly higher when assessed by ZVA-INS (3990±1795 dynes.s.cm³) than VAL (946±318 dynes.s.cm³) (R=0.941; R²=0.886; F=109.2; P

INTRODUCTION Ventricular function in elderly patients with aortic stenosis is impeded both by restricted aortic flow and arterial stiffening. A number of patients continue to have exertional intolerance after relief of aortic valvular obstruction due to unrecognized ventriculo-arterial coupling mismatch. HYPOTHESIS Quantification of valvulo-arterial load (VAL), using a simultaneous applanation tonometry/cardiac magnetic resonance (CMR) technique, can accurately assess the relative contributions of aortic stiffness and valve gradient in older patients with aortic stenosis. METHODS Elderly patients with aortic stenosis underwent a simultaneous applanation tonometry/CMR protocol. CMR provided left ventricular volume and aortic flow simultaneously with radial applanation tonometry pressure acquisition. Central aortic pressure was derived by transformation of the radial applanation tonometry waveform. VAL was determined as the relationship of derived aortic pressure to CMR aortic flow in frequency domain (central illustration). RESULTS Twenty patients (age 80 ± 9 years; 12 males; blood pressure 140/75 ± 20 mmHg) with aortic stenosis on transthoracic echocardiogram (16 severe; mean gradient 45 ± 16 mmHg; aortic valve area 0.8 ± 0.2 cm2) were enrolled. Derived aortic pressure and flow waveforms correlated well with invasive data. Increased VAL was significantly associated with advanced age (P = 0.04) and raised SBP (P

Arterial stiffness is an important predictor of cardiovascular events, independent of traditional risk factors. Stiffening of arteries, though an adaptive process to hemodynamic load, results in substantial increase in the pulsatile hemodynamic forces that detrimentally affects the microcirculation perfusing the vital organs such as the brain, heart and kidneys. Studies have proposed that arterial stiffness precedes and may contribute to the development of hypertension in individuals with obesity. Our study sought to determine the gender-based effects on arterial stiffening in obesity which may predispose to the development of hypertension. We found female sex is associated with higher susceptibility of weight-related arterial stiffening and rise in blood pressure in obesity. Women had significantly higher carotid-femoral pulse wave velocity (CF-PWV) with higher body mass index (BMI) status (normal: 7.9 ± 2 m/s, overweight: 9.1 ± 2 m/s, obese: 9 ± 2 m/s, p &lt, 0.001), whereas it was similar in males across all BMI categories. The linear association between arterial stiffness and BMI following adjustment for age and brachial systolic and diastolic blood pressure (BP), remained significant in females (β = 0.06, 95% CI 0.01 to 0.1, p &lt, 0.05) but not in males (β = 0.04, 95% CI −0.01 to 0.1, p &gt, 0.05). The mean CF-PWV values increased by 0.1 m/s for every 1 kg/m2 increase in BMI in the female subjects in the age adjusted linear model, while such effect was not seen in the male subjects. In line with arterial stiffening, the overweight and obese females demonstrated significantly higher systolic brachial BP. (BP difference: ΔBP 9−11 mmHg, p &lt, 0.01) and central systolic pressure (ΔBP 8−10 mmHg, p &lt, 0.05) compared to their lean counterparts, unlike the male subjects. Our results suggest that female gender is associated with higher susceptibility of weight-related arterial stiffening and rise in blood pressure.

Purpose Hemolysis is an important complication of ventricular assist device (VAD) therapy. Several studies have postulated that chronic hemolysis may be a cause of adverse outcomes in patients with VADs, but consistent definitions and clinical outcome data are lacking. Methods We conducted a single-center retrospective cohort study examining survival to transplantation in patients who underwent VAD implantation from 2010-2020. Baseline demographics, renal function, echocardiographic, and cardiac catheterization data for the first 12 months of VAD therapy or until transplantation were collected. Additionally, all available lactate dehydrogenase (LDH) values were collected over this time frame and means were calculated for each patient. Results VADs were implanted in 166 patients, 19% female and 87% left-sided devices. Patients with mean LDH above the upper limit of normal for our laboratory's LDH assay of 440 units/liter (U/L) were more likely to die prior to transplantation compared to those with mean LDH Conclusion Mean LDH above the normal range was an independent and significant predictor of mortality in patients with VADs awaiting transplantation at our center over the last decade. While concomitant severe liver or RV dysfunction can raise LDH, chronic hemolysis is an important potential etiology for our observations. Further work is needed to define chronic hemolysis and its impact on outcomes in patients with VADs.

Background: Aortic stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload, but rather, functions as a series circuit, with important contributions from both the valve and vasculature. Patients with AS are typically elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizeable, and yet, quantifying this to-date has been difficult to determine. We compared measurement of aortic pressure, flow and global LV load using a cardiac magnetic resonance (CMR)/applanation tonometry (AT) technique to uncouple ventriculo-arterial (VA) interactions. Methods: 20 healthy elderly patients and 20 with AS underwent a CMR/AT protocol. CMR provided LV volume and aortic flow simultaneously with AT pressure acquisition. Aortic pressure was derived by transformation of the AT waveform. Systemic vascular resistance (SVR) and global LV load were determined as the relationship of pressure to flow in the frequency domain. Values from both cohorts were compared. Results: AS patients were older (p ​

Aortic valve stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload (due to an obstructive valve), but rather, functions as a series circuit with important contributions from both the valve and ageing vasculature. Patients with AS are frequently elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizable, and yet, the contribution of ventricular afterload has been difficult to determine. Arterial stiffening increases the speed of propagation of the blood pressure wave along the central arteries (estimated as the pulse wave velocity), which results in an earlier return of reflected waves. The effect is to augment blood pressure in the proximal aorta during systole, increasing the central pulse pressure and, in turn, placing even greater afterload on the heart. Elevated global LV afterload is known to have adverse consequences on LV remodelling, function and survival in patients with AS. Consequently, there is renewed focus on methods to estimate the relative contributions of local versus global changes in arterial mechanics and valvular haemodynamics in patients with AS. We present a review on existing and upcoming methods to quantify valvulo-arterial impedance and thereby global LV load in patients with AS.

Introduction: Valvuloarterial impedance (Z VA ) represents the valvular and arterial factors that oppose Left Ventricular (LV) ejection and is recognised as an important index to assess global LV load in patients with Aortic Stenosis (AS). Z VA is traditionally determined by Transthoracic Echocardiogram (TTE) and brachial cuff pressure. Hypothesis: Our study sought to compare Z VA-TTE with Z VA calculated using a simultaneous Cardiac Magnetic Resonance (CMR) and Applanation Tonometry (AT) (Z VA-CMR ) technique to determine whether TTE measurement of aortic flow velocity resulted in an underestimation of Z VA. Methods: Twenty AS patients underwent a protocol of CMR/AT followed by TTE. Z VA-CMR was determined as the relationship of derived aortic pressure (radial) to CMR aortic flow velocity in the frequency domain. Z VA-TTE was determined from digitised flow velocity within the left ventricular outflow tract (LVOT) on pulsed-wave Doppler and derived central pressure waveforms. Systemic vascular resistance (SVR) was calculated from mean pressure and flow. Values from both methods were compared. Results: Our study found that Z VA-TTE values (mean±SD, 638±381 dyne.s.cm -3 ) were consistently lower (p=0.07) than Z VA-CMR values (946±318 dyne.s.cm -3 ), and attribute this to an overestimation of LVOT flow velocity on TTE. SVR calculated by CMR/AT (2215±616 dyne.s.cm -5 ) was almost four times higher than TTE (618±245 dyne.s.cm -5 ) (p Conclusions: Whilst Z VA -TTE is commonly performed in patients with AS to assess global LV load, newer methods to assess Z VA using simultaneous CMR/AT likely represent a more accurate non-invasive assessment.

Background Although it has been established that continuous flow left ventricular assist devices are sensitive to loading conditions, the effect of acute load and postural changes on pump flow have not been explored systematically. Methods and Results Fifteen stable outpatients were studied. Patients sequentially transitioned from the seated position to supine, passive leg raise, and standing with transition effects documented. A modified Valsalva maneuver, consisting of a forced expiration with an open glottis, was performed in each position. A sustained, 2-handed handgrip was performed in the supine position. The pump flow waveform was recorded continuously and left ventricular end-diastolic diameter measured during each stage using transthoracic echocardiography. Transitioning from seated to supine posture produced a significant increase in the flow and the ventricular end-diastolic diameter, consistent with an increased preload. The transition from supine to standing produced a transient increase in the mean flow and decreased the flow pulsatility index. At steady state, these changes were reversed with a decrease in the mean and trough flow and increased pulsatility index, consistent with venous redistribution and possible baroreflex compensation. Four distinct patterns of standing-induced flow waveform effects were identified, reflecting varying preload, afterload, and individual compensatory effects. A sustained handgrip produced a significant decrease in flow and increase in flow pulsatility across all patients, reflecting an increased afterload pressure. A modified Valsalva maneuver produced a decrease in the flow pulsatility while seated, supine, and standing, but not during leg raise. Five patterns of pulsatility effect during Valsalva were observed: (1) minimal change, (2) pulsatility recovery, (3) rapid flatline, (4) slow flatline with delayed flow recovery, and (5) primary suction. Conclusions Acute disturbances in loading conditions produce heterogeneous pump flow responses reflecting their complex interactions with pump and ventricular function as well as reflex compensatory mechanisms. Differences in responses and individual variabilities have significant implications for automated pump control algorithms.

Purpose Renal function following ventricular assist device (VAD) implantation is a key determinant of survival. The purpose of our study was to investigate whether the development of acute kidney injury (AKI) prior to, or following, VAD implantation influenced survival to transplant. We also sought to determine if the use of extra-corporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) influenced AKI pre or post-VAD. Methods We undertook a single-centre retrospective cohort study examining outcomes in patients who underwent VAD implantation between 2010 and 2020. AKI was defined as per the KDIGO guidelines. The primary outcome was survival to transplant. Results 61% (96/158) of patients experienced pre-VAD AKI which predicted an increased risk of mortality (OR 2.32, p=0.032, CI 1.07 - 5.04). The incidence of post-VAD AKI was 54% (89/165) which was similarly associated with an increased risk of mortality (OR 2.49, p=0.012, CI 1.21 - 5.13). 67% (64/96) of patients who experienced pre-VAD AKI had post-VAD AKI. Patients who had both pre and post-VAD AKI had a significantly increased mortality prior to transplant with an OR of 3.5 (P=0.01, CI 1.3 - 9.41). Patients with pre-VAD AKI were more likely to require ECMO prior to VAD implantation (OR 2.94) however no difference was observed for IABP use. The use of ECMO or IABP prior to VAD implantation did not influence post-VAD AKI. Conclusion Acute kidney injury both pre and post-VAD implantation reduced likelihood of survival to transplant. Patients with AKI prior to VAD insertion were more likely to require ECMO, however the use of ECMO or IABP pre-VAD insertion did not appear to influence post-VAD AKI.

BACKGROUND Cerebral syndromes in older humans, secondary stroke in younger persons following trauma, and sickle cell anaemia in children, are linked by unexplained microvascular damage and high cerebral pressure or flow pulsations. The aim of this study was to characterize age-related pressure and flow waveforms patterns entering the brain, to explain these in terms of disturbed physiological function, and to consider clinical implications. METHOD Blood flow velocity waves were measured in four cerebral vascular territories by transcranial Doppler of 1020 apparently normal patients (497 men, 21-78 years). Central pressure waveforms were generated from radial artery applanation tonometry with SphygmoCor. Relationships were described in time and frequency domains. RESULTS AND CONCLUSION Flow waveforms entering the brain showed similar pattern to central aortic pressure waveforms, and similar changes with age. Augmentation index of flow and of pressure had high correlation at different ages, and in men and women (r = 0.58, P

BACKGROUND: Uncontrolled hypertension (HTN) is a leading modifiable stroke risk factor contributing to global stroke disparities. This study is unique in testing a transitional care model aimed at controlling HTN in black and Hispanic poststroke, home health patients, an understudied group. METHODS: A 3-arm randomized controlled trial design compared (i) usual home care (UHC), with (ii) UHC plus a 30-day nurse practitioner transitional care program, or (iii) UHC plus nurse practitioner plus a 60-day health coach program. The trial enrolled 495 black and Hispanic, English- and Spanish- speaking adults with uncontrolled systolic blood pressure (SBP ≥ 140 mm Hg) who had experienced a first-time or recurrent stroke or transient ischemic attack. The primary outcome was change in SBP from baseline to 3 and 12 months. RESULTS: Mean participant age was 67; 57.0% were female; 69.7% were black, non-Hispanic; and 30.3% were Hispanic. Three-month follow-up retention was 87%; 12-month retention was 81%. SBP declined 9–10 mm Hg from baseline to 12 months across all groups; the greatest decrease occurred between baseline and 3 months. The interventions demonstrated no relative advantage compared to UHC. CONCLUSION: The significant across-the-board SBP decreases suggest that UHC nurse/patient/physician interactions were the central component of SBP reduction and that additional efforts to lower recurrent stroke risk should test incremental improvements in usual care, not resource-intensive transitional care interventions. They also suggest the potential value of pragmatic home care programs as part of a broader strategy to overcome HTN treatment barriers and improve secondary stroke prevention globally. CLINICAL TRIALS REGISTRATION: Trial Number NCT01918891.