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Monitoring for thrombosis and hemolysis is crucial for patients under extracorporeal or mechanical circulatory support, but it can be costly. We investigated correlations between hemolysis index (HI) and plasma-free hemoglobin (PFH) levels on one hand, and between the HI and plasma lactate dehydrogenase (LDH) levels on the other, in critically ill patients with and without extracorporeal or mechanical circulatory support. Additionally, we calculated the cost reductions if monitoring through HI were to replace monitoring through PFH or plasma LDH. In a single-center study, HI was compared with PFH and plasma LDH levels in blood samples taken for routine purposes in critically ill patients with and without extracorporeal or mechanical circulatory support. A cost analysis, restricted to direct costs associated with each measurement, was made for an average 10-bed ICU. This study included 147 patients: 56 patients with extracorporeal or mechanical circulatory support (450 measurements) and 91 patients without extracorporeal or mechanical circulatory support (562 measurements). The HI correlated well with PFH levels (r = 0.96; p < 0.01) and poorly with plasma LDH levels (r = 0.07; p < 0.01) in patients with extracorporeal or mechanical circulatory support. Similarly, HI correlated well with PFH levels (r = 0.97; p < 0.01) and poorly with plasma LDH levels (r = −0.04; p = 0.39) in patients without extracorporeal or mechanical circulatory support. ROC analyses demonstrated a strong performance of HI, with the curve indicating excellent discrimination in the whole cohort (area under the ROC of 0.969) as well as in patients under ECMO or mechanical circulatory support (area under the ROC of 0.988). Although the negative predictive value of HI for predicting PFH levels > 10 mg/dL was high, its positive predictive value was found to be poor at various cutoffs. A simple cost analysis showed substantial cost reduction if HI were to replace PFH or plasma LDH for hemolysis monitoring. In conclusion, in this cohort of critically ill patients with and without extracorporeal or mechanical circulatory support, HI correlated well with PFH levels, but poorly with plasma LDH levels. Given the high correlation and substantial cost reductions, a strategy utilizing HI may be preferable for monitoring for hemolysis compared to monitoring strategies based on PFH or plasma LDH. The PPV of HI, however, is unacceptably low to be used as a diagnostic test.

Introduction: Ventricular assist devices (LVADs) are a valuable therapy for end-stage heart failure patients. However, some adverse events still persist, such as suction that can trigger thrombus formation and cardiac rhythm disorders. The aim of this study is to validate a suction module (SM) as a test bench for LVAD suction detection and speed control algorithms.Methods: The SM consists of a latex tube, mimicking the ventricular apex, connected to a LVAD. The SM was implemented into a hybrid in vitro-in silico cardiovascular simulator. Suction was induced simulating hypovolemia in a profile of a dilated cardiomyopathy and of a restrictive cardiomyopathy for pump speeds ranging between 2,500 and 3,200 rpm. Clinical data collected in 38 LVAD patients were used for the validation. Clinical and simulated LVAD flow waveforms were visually compared. For a more quantitative validation, a binary classifier was used to classify simulated suction and non-suction beats. The obtained classification was then compared to that generated by the simulator to evaluate the specificity and sensitivity of the simulator. Finally, a statistical analysis was run on specific suction features (e.g., minimum impeller speed pulsatility, minimum slope of the estimated flow, and timing of the maximum slope of the estimated flow).Results: The simulator could reproduce most of the pump waveforms observed in vivo. The simulator showed a sensitivity and specificity and of 90.0% and 97.5%, respectively. Simulated suction features were in the interquartile range of clinical ones.Conclusions: The SM can be used to investigate suction in different pathophysiological conditions and to support the development of LVAD physiological controllers.

Atrial fibrillation (AF) is a common comorbidity in left ventricular assist device (LVAD) patients and has been identified as a risk factor for thromboembolic stroke. Blood stagnation within the left atrial appendage (LAA) is considered a possible major source of thrombosis and clinical studies have shown reduced thromboembolic risk after LAA occlusion (LAAO). Therefore, this study aims to investigate the effect of LAAO on thrombosis-related parameters using patient-specific simulations. Left ventricular and left atrial geometries of an LVAD patient were obtained from computed tomography and combined with hemodynamic data with either sinus rhythm (SR) or AF generated by a lumped parameter model. In four simulations applying contractile walls, stagnation volume and blood residence times were evaluated with or without AF and with or without LAAO. Reduced atrial contraction in AF resulted in unfavorable flow dynamics within the left atrium. The average atrial velocity was lower for the AF simulation when compared to SR, resulting in a 55% increase in the atrial stagnation volume (from 4.2 to 6.5 cm3). Moreover, blood remained in the LAA for more than 8 cardiac cycles. After LAAO the atrial stagnation decreased from 4.2 to 1.4 cm3 for SR and from 6.5 to 2.3 cm3 for the AF simulation. A significant stagnation volume was found in the LAA for both SR and AF, with larger values occurring with AF. These regions are known as potential sources for thrombus formation and can be diminished by LAAO. This significantly improved the thrombus-related flow parameters and may also lower the risk of thromboembolic events from the appendage.

Background: Mechanical circulatory support (MCS) in pediatric patients remains challenging because of small body size, limited availability of approved devices, and the variety of etiologies, including biventricular and univentricular physiologies. We report our single-center experience with MCS in pediatric patients in terms of survival and adverse events. Methods: Outcome, etiologic, and demographic data of pediatric patients implanted with a long-term MCS device between 2011 and 2019 at the Medical University of Vienna were retrospectively collected and analyzed. Overall survival and freedom of treatment-related adverse events at 1 year were investigated by Kaplan–Meier analyses and stratified for circulation (biventricular vs univentricular), age group (6 years), and pump technology (pulsatile ventricular assist device [p-VAD] vs continuous flow pump [cf-VAD]). Results: One-year survival of all 33 pediatric patients (median, 4 years; interquartile range, 0-13 years) was 73%, with a tendency toward better outcomes in patients with biventricular circulation than in those with univentricular circulation (80%; n = 25 vs 50%; n = 8; P = .063). The trends toward better survival probability in older patients and in patients with cf-VADs did not reach statistical significance (63.2% vs 85.7%; P = .165 and 82.4% vs 62.5%; P = .179, respectively). Freedom from adverse events was higher in older patients (57.1% vs 5.6%; P

Reduced oxygen consumption (VO2), either due to insufficient oxygen delivery (DO2), microcirculatory hypoperfusion and/or mitochondrial dysfunction, has an impact on the adverse short- and long-term survival of patients after cardiac surgery. However, it is still unclear whether VO2 remains an efficient predictive marker in a population in which cardiac output (CO) and consequently DO2 is determined by a left ventricular assist device (LVAD). We enrolled 93 consecutive patients who received an LVAD with a pulmonary artery catheter in place to monitor CO and venous oxygen saturation. VO2 and DO2 of in-hospital survivors and non-survivors were calculated over the first 4 days. Furthermore, we plotted receiver-operating curves (ROC) and performed a cox-regression analysis. VO2 predicted in-hospital, 1- and 6-year survival with the highest area under the curve of 0.77 (95%CI: 0.6–0.9; p = 0.0004). A cut-off value of 210 mL/min VO2 stratified patients regarding mortality with a sensitivity of 70% and a specificity of 81%. Reduced VO2 was an independent predictor for in-hospital, 1- and 6-year mortality with a hazard ratio of 5.1 (p = 0.006), 3.2 (p = 0.003) and 1.9 (p = 0.0021). In non-survivors, VO2 was significantly lower within the first 3 days (p = 0.010, p < 0.001, p < 0.001 and p = 0.015); DO2 was reduced on days 2 and 3 (p = 0.007 and p = 0.003). In LVAD patients, impaired VO2 impacts short- and long-term outcomes. Perioperative and intensive care medicine must, therefore, shift their focus from solely guaranteeing sufficient oxygen supply to restoring microcirculatory perfusion and mitochondrial functioning.

BackgroundContemporary Left Ventricular Assist Devices (LVADs) mainly operate at a constant speed, only insufficiently adapting to changes in patient demand. Automatic physiological speed control promises tighter integration of the LVAD into patient physiology, increasing the level of support during activity and decreasing support when it is excessive.MethodsA sensorless modular control algorithm was developed for a centrifugal LVAD (HVAD, Medtronic plc, MN, USA). It consists of a heart rate-, a pulsatility-, a suction reaction—and a supervisor module. These modules were embedded into a safe testing environment and investigated in a single-center, blinded, crossover, clinical pilot trial (clinicaltrials.gov, NCT04786236). Patients completed a protocol consisting of orthostatic changes, Valsalva maneuver and submaximal bicycle ergometry in constant speed and physiological control mode in randomized sequence. Endpoints for the study were reduction of suction burden, adequate pump speed and flowrate adaptations of the control algorithm for each protocol item and no necessity for intervention via the hardware safety systems.ResultsA total of six patients (median age 53.5, 100% male) completed 13 tests in the intermediate care unit or in an outpatient setting, without necessity for intervention during control mode operation. Physiological control reduced speed and flowrate during patient rest, in sitting by a median of −75 [Interquartile Range (IQR): −137, 65] rpm and in supine position by −130 [−150, 30] rpm, thereby reducing suction burden in scenarios prone to overpumping in most tests [0 [−10, 2] Suction events/minute] in orthostatic upwards transitions and by −2 [−6, 0] Suction events/min in Valsalva maneuver. During submaximal ergometry speed was increased by 86 [31, 193] rpm compared to constant speed for a median flow increase of 0.2 [0.1, 0.8] L/min. In 3 tests speed could not be increased above constant set speed due to recurring suction and in 3 tests speed could be increased by up to 500 rpm with a pump flowrate increase of up to 0.9 L/min.ConclusionIn this pilot study, safety, short-term efficacy, and physiological responsiveness of a sensorless automated speed control system for a centrifugal LVAD was established. Long term studies are needed to show improved clinical outcomes.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04786236.

Background: Risk factors for driveline infection (DLI) in patients with left ventricular assist devices are multifactorial. The aim of this study was to analyze the correlation between mechanical driveline features and DLI occurrence.Methods: A meta-analysis was conducted that included studies reporting DLI rates at 6 months after implantation of any of three contemporary devices (HVAD with Pellethane or Carbothane driveline, HeartMate II, and HeartMate 3). Further, outer driveline diameter measurements and ex-vivo experimental three-point bending and torsion tests were performed to compare the stiffness of the four different driveline types.Results: 21 studies with 5,393 patients were included in the meta-analysis. The mean weighted DLI rates ranged from 7.2% (HeartMate II) to 11.9% (HeartMate 3). The HeartMate II driveline had a significantly lower maximal bending force (Loadmax) (4.52 ± 0.19 N) compared to the Carbothane HVAD (8.50 ± 0.08 N), the HeartMate 3 (11.08 ± 0.3 N), and the Pellethane HVAD driveline (15.55 ± 0.14 N) (p < 0.001). The maximal torque (Torquemax) of the HeartMate II [41.44 (12.61) mNm] and the Carbothane HVAD driveline [46.06 (3.78) mNm] were significantly lower than Torquemax of the Pellethane HVAD [46.06 (3.78) mNm] and the HeartMate 3 [95.63 (26.60) mNm] driveline (p < 0.001). The driveline of the HeartMate 3 had the largest outer diameter [6.60 (0.58) mm]. A relationship between the mean weighted DLI rate and mechanical driveline features (Torquemax) was found, as the the HeartMate II driveline had the lowest Torquemax and lowest DLI rate, whereas the HeartMate 3 driveline had the highest Torquemax and highest DLI rate.Conclusions: Device-specific mechanical driveline features are an additional modifiable risk factor for DLI and may influence clinical outcomes of LVAD patients.

Advanced stage heart failure patients can benefit from the unloading effects of an implantable left ventricular assist device. Despite best clinical practice, LVADs are associated with adverse events, such as pump thrombosis (PT). An adaptive algorithm alerting when an individual’s appropriate levels in pump power uptake are exceeded, such as in the case of PT, can improve therapy of patients implanted with a centrifugal LVAD. We retrospectively studied 75 patients implanted with a centrifugal LVAD in a single center. A previously optimized adaptive pump power-tracking algorithm was compared to clinical best practice and clinically available constant threshold algorithms. Algorithm performances were analyzed in a PT group (n = 16 patients with 30 PT events) and a thoroughly selected control group (n = 59 patients, 34.7 patient years of LVAD data). Comparison of the adaptive power-tracking algorithm with the best performing constant threshold algorithm resulted in sensitivity of 83.3% vs. 86.7% and specificity of 98.9% vs. 95.3%, respectively. The power-tracking algorithm produced one false positive detection every 11.6 patient years and early warnings with a median of 3.6 days prior to PT diagnosis. In conclusion, a retrospective single-center validation study with real-world patient data demonstrated advantageous application of a power-tracking algorithm into LVAD systems and clinical practice.

Right heart failure (RHF) is a severe complication after left ventricular assist device (LVAD) implantation. The aim of this study was to analyze the incidence, risk factors, and biomarkers for late RHF including the possible superiority of the device and implantation method. This retrospective, single-center study included patients who underwent LVAD implantation between 2014 and 2018. Primary outcome was freedom from RHF over one-year after LVAD implantation; secondary outcomes included pre- and postoperative risk factors and biomarkers for RHF. Of the 145 consecutive patients (HeartMate 3/HVAD: n = 70/75; female: 13.8%), thirty-one patients (21.4%) suffered RHF after a mean LVAD support of median (IQR) 105 (118) days. LVAD implantation method (less invasive: 46.7% vs. 35.1%, p = 0.29) did not differ significantly in patients with or without RHF, whereas the incidence of RHF was lower in HeartMate 3 vs. HVAD patients (12.9% vs. 29.3%, p = 0.016). Multivariate Cox proportional hazard analysis identified HVAD (HR 4.61, 95% CI 1.12–18.98; p = 0.03), early post-op heart rate (HR 0.96, 95% CI 0.93–0.99; p = 0.02), and central venous pressure (CVP) (HR 1.21, 95% CI 1.05–1.39; p = 0.01) as independent risk factors for RHF, but no association of RHF with increased all-cause mortality (HR 1.00, 95% CI 0.99–1.01; p = 0.50) was found. To conclude, HVAD use, lower heart rate, and higher CVP early post-op were independent risk factors for RHF following LVAD implantation.

BACKGROUND:Left ventricular assist devices (LVADs) are an established treatment for end stage heart failure patients. As LVADs do not currently respond to exercise demands, attention is also directed towards improvements in exercise capacity and resulting quality of life. The aim of this study was to explore hemodynamic responses observed during maximal exercise tests to infer underlying patient status and therefore investigate possible diagnostics from LVAD derived data and advance the development of physiologically adaptive LVAD controllers. METHODS:High resolution continuous LVAD flow waveforms were recorded from 14 LVAD patients and evaluated at rest and during maximum bicycle exercise tests (n = 24). Responses to exercise were analyzed in terms of an increase (↑) or decrease (↓) in minimum (QMIN), mean (QMEAN), maximum flow (QMAX) and flow pulsatility (QP2P). To interpret clinical data, a cardiorespiratory numerical simulator was used that reproduced patients' hemodynamics at rest and exercise. Different cardiovascular scenarios including chronotropic and inotropic responses, peripheral vasodilation, and aortic valve pathologies were simulated systematically and compared to the patients' responses. RESULTS:Different patients' responses to exercise were observed. The most common response was a positive change of ΔQMIN↑ and ΔQP2P↑ from rest to exercise (70% of exercise tests). Two responses, which were never reported in patients so far, were distinguished by QMIN↑ and QP2P↓ (observed in 17%) and by QMIN↓ and QP2P↑ (observed in 13%). The simulations indicated that the QP2P↓ can result from a reduced left ventricular contractility and that the QMIN↓ can occur with a better left ventricular contractility and/or aortic insufficiency. CONCLUSION:LVAD flow waveforms determine a patients' hemodynamic "fingerprint" from rest to exercise. Different waveform responses to exercise, including previously unobserved ones, were reported. The simulations indicated the left ventricular contractility as a major determinant for the different responses, thus improving patient stratification to identify how patient groups would benefit from exercise-responsive LVAD control.

Several risk scores and classifications are available to predict peri- and post-operative mortality of patients with end stage heart failure receiving Left Ventricular Assist Device (LVAD) therapy. Sarcopenia has been suggested as a sensitive predictor for post-operative mortality. We evaluated whether the psoas muscle area can predict mortality in patients undergoing LVAD implantation. The indexed psoas mean area (PMAi) was obtained by measuring the psoas muscle area at the superior endplate of the third lumbar vertebra correlated to body surface area of 106 adult patients undergoing LVAD implantation (Medtronic HVAD n = 41, Abbott HeartMate II n = 4, Abbott HeartMate 3 n = 61; mean age 65, IQR 12, 90.6% male; INTERMACS Level 1 24.5%; ischemic CMP 64.2%). Patients were divided in two groups: high/moderate and low muscle mass. The primary endpoint was 30-day mortality, assessed using a multivariate Cox proportional hazards model. Baseline characteristics did not differ between patients with high or moderate and low PMAi. Estimated survival calculated a significant higher 30-day mortality in patients with low PMAi (p = 0.04). Multivariable Cox proportional hazards regression analysis indicated low PMAi, history of previous cardiac surgery and levels of bilirubin as independent predictors of mortality in the first 30 days. In conclusion, indexed psoas muscle area predicts mortality after LVAD implantation and can be used as an additional tool for risk stratification.