Sixth INTERMACS annual report: a 10,000-patient database.

The sixth annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 8 years of patient enrollment. The analysis is based on data from >10,000 patients and updates demographics, survival, adverse events and risk factors. Among patients with continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70% at 2 years. The report features a comparison of two eras of continuous-flow durable devices in the USA in terms of device strategy, patient profiles, adverse event burden, survival and quality of life.

Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device.

BACKGROUND: Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. METHODS: Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis. RESULTS: Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant. CONCLUSIONS: Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HMII LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis.

Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients.

The 5th annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 6 years of patient and data collection. The current analysis includes more than 6000 patients and updated risk factors for continuous flow pumps. Among continuous flow pumps, actuarial survival is 80% at 1 year and 70% at 2 years. Quality of life indicators are generally favorable and adverse event burden will likely influence patient selections of advanced heart failure therapies.

Novel engineering approaches to obesity, overweight, and energy balance: public health needs and research opportunities.

The obesity epidemic is one of the most rapidly evolving public health problems of our day. At present, 2/3 of American adults and 1/6 of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high and reflects documented increased risk of cardiovascular disease, type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis, and increased mortality from these ailments, especially among the most obese. Innovative engineering technologies are needed to address a large range of problems in energy balance, intake, and expenditure that are associated with the obesity epidemic. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Novel sensors, devices, imaging technologies, nanotechnology, biomaterials, and other approaches need to be developed and evaluated through multidisciplinary collaborations between engineers, physical scientists, and scientists with expertise in obesity and nutrition. The goal is to encourage research to develop useful technologies and tools to facilitate research and eventually to support therapeutic advances and behavioral change. Furthermore, the possibility of re-engineering the "built environment" to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov).

Fluid dynamics of the CarboMedics kinetic bileaflet prosthetic heart valve.

OBJECTIVE: To compare hydrodynamic characteristics of a new bileaflet heart valve, the CarboMedics kinetic cardiac valve prosthesis, with those of a St. Jude Medical (SJM) heart valve. METHODS: Hydrodynamic characteristics were determined in the mitral and aortic positions of a Vivitro Systems pulse duplicator for size 23 Kinetic aortic values, size 23 SJM aortic valves, size 29 Kinetic mitral valves and size 29 SJM mitral valves. Test conditions were 72 beats per min with cardiac outputs of 2, 5 and 7 l/min. Values of forward flow pressure drop (delta P), regurgitant and energy loss were determined for each valve. The test results for the two valve designs were compared by valve size. RESULTS: The test results show that both the size 23 and size 29 Kinetic valves have 8-14% lower delta P values and 5-10% greater effective orifice area (EOA) values. The size 29 Kinetic mitral valve has a 1-2 ml lower regurgitant volume, while the size 23 Kinetic aortic valve has a 0.5 ml greater regurgitant volume than the corresponding SJM values. These factors combine to provide a 5-10% lower energy loss for size 23 Kinetic aortic valves and a 15-25% lower energy loss for size 29 Kinetic mitral valves over the cardiac cycle than for corresponding sizes of SJM valves. CONCLUSIONS: The Kinetic valve's fluid dynamics are superior to equivalent sizes of SJM valves. This is especially impressive considering that the tissue annulus diameters for Kinetic valves are approximately 0.5 mm less than equivalent size SJM valves. The primary reasons for the superior hydrodynamic performance of Kinetic valves are (1) the larger orifices which result in lower forward flow delta P values and (2) the opening angles, which have been customized for each valve size to minimize energy loss.

LDA measurements of mean velocity and Reynolds stress fields within an artificial heart ventricle.

Laser Doppler Anemometry measurements of mean (ensemble average) velocities and turbulent (Reynolds) stresses at 140 locations within the left ventricle of the Penn State 70 cc electric artificial heart/ventricular assist device are reported at 8 times during the cardiac cycle. Mean velocity patterns indicate that the surfaces of the blood sac and valve tracts are exposed to significant levels of wall shear stress (good wall washing) during some portion of the flow cycle, and there is no location where the flow is stagnant over the entire flow cycle. This implies that thrombus deposition within the artificial heart should be suppressed. Turbulent stresses in the main pumping chamber and the outflow tracts of the tilting disk valves do not exceed 2000 dynes/cm2. The highest turbulent stresses (20,000 dynes/cm2) and smallest turbulent microscales (6 microns) are found in the regurgitant jets on the minor orifice side of the aortic valve during diastole and the mitral valve during systole. Taken together, the data suggest that improvements in artificial heart fluid mechanics will come through valve design and pump operating conditions, not pumping chamber design.

Determination of principal reynolds stresses in pulsatile flows after elliptical filtering of discrete velocity measurements.

The purpose of this study was to develop a method to accurately determine mean velocities and Reynolds stresses in pulsatile flows. The pulsatile flow used to develop this method was produced within a transparent model of a left ventricular assist device (LVAD). Velocity measurements were taken at locations within the LVAD using a two-component laser Doppler anemometry (LDA) system. At each measurement location, as many as 4096 realizations of two coincident orthogonal velocity components were collected during preselected time windows over the pump cycle. The number of realizations was varied to determine how the number of data points collected affects the accuracy of the results. The duration of the time windows was varied to determine the maximum window size consistent with an assumption of pseudostationary flow. Erroneous velocity realizations were discarded from individual data sets by implementing successive elliptical filters on the velocity components. The mean velocities and principal Reynolds stresses were determined for each of the filtered data sets. The filtering technique, while eliminating less than 5 percent of the original data points, significantly reduced the computed Reynolds stresses. The results indicate that, with proper filtering, reasonable accuracy can be achieved using a velocity data set of 250 points, provided the time window is small enough to ensure pseudostationary flow (typically 20 to 40 ms). The results also reveal that the time window which is required to assume pseudostationary flow varies with location and cycle time and can range from 100 ms to less than 20 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Mean velocities and Reynolds stresses within regurgitant jets produced by tilting disc valves.

Fluid velocities were measured with a two-component laser Doppler anemometry system in the regurgitant jet regions of Bjork-Shiley Delrin monostrut tilting disc valves mounted within a Plexiglas model of the 70 cm3 Penn State electric left ventricular assist device. At each measurement location, 250 instantaneous velocity realizations were collected at times when regurgitation through the valves occurred. The maximum Reynolds shear and normal stresses were calculated after filtering the data. Results show that Reynolds shear and normal stresses proximal to the mitral valve were elevated to magnitudes of 9,000 dynes/cm2 and 20,000 dynes/cm2, respectively. The peak Reynolds stresses near the mitral valve occurred during early systole, when regurgitant jet velocities reached magnitudes as high as 440 cm/sec. The Reynolds shear and normal stresses proximal to the aortic valve reached magnitudes of 9,900 dynes/cm2 and 20,500 dynes/cm2, respectively. The peak Reynolds stresses near the aortic valve occurred during early diastole, when regurgitant jet velocities were as high as 280 cm/sec. These high Reynolds stresses created by turbulent regurgitant flow have the potential to cause significant blood damage.

Estimation of Reynolds stresses within the Penn State left ventricular assist device.

Fluid velocities were measured using a two-component laser Doppler anemometery (LDA) system at 129 locations within a Plexiglas model of a 70 cm3 Penn State electric Left Ventricular Assist Device (LVAD). The LVAD was driven by a pulsatile piston pump acting on an attached segmented polyurethane diaphragm. Bjork-Shiley tilting disc valves were used to provide unidirectional flow through the inlet and outlet ports. A seeded blood analog fluid, which matched the kinematic viscosity of blood at high shear rates and the refractive index of Plexiglas, was used to make the measurements. At each location, 250 instantaneous velocity realizations were collected at eight instances during the pump cycle. The maximum Reynolds shear and normal stresses were calculated for each pump cycle time and location after filtering the data. The results reveal that the highest Reynolds shear and normal stresses occur in the near wall region just proximal to the aortic valve during diastole, and reach values of 5,300 dynes/cm2 and 10,800 dynes/cm2, respectively. The elevated turbulent stresses are observed during the period of regurgitant flow through the aortic valve, with peak stress values arising during the period of peak regurgitant flow. This supports the hypothesis that a regurgitant turbulent jet is formed near the wall of the prosthetic aortic valve and may be contributing to blood damage.

Mean flow velocity patterns within a ventricular assist device.

A laser Doppler anemometry system was used to measure fluid velocities at 127 locations within a plexiglas model of the 70 cm3 Penn State electric ventricular assist device (VAD) fitted with Bjork-Shiley convexo-concave tilting disk valves. The velocity measurements were made using a seeded blood analog fluid that matched the kinematic viscosity of blood and the refractive index of plexiglas. At each location, 250 instantaneous velocity realizations were collected at eight instances during the pump cycle. The data were filtered and averaged to calculate mean (ensemble averaged) velocities. The results indicate that the largest mean velocities are created during systole in the VADs outlet tract, and during diastole in the major orifice of the mitral valve. A single vortex centered roughly about the axis of the cylindrical portion of the pump is created during early diastole. This vortex, which persists into early systole, provides good washing of the VAD walls. However, it does appear to impede the flow entering the VAD through the minor orifice of the mitral valve. High velocities also occur during diastole along the minor orifice wall of the outlet tract and are directed into the chamber. These retrograde velocities suggest the presence of a regurgitant jet near the wall of the prosthetic valve.

Hot-film wall shear probe measurements inside a ventricular assist device.

Wall shear rates at eleven sites within the Penn State Electric Ventricular Assist Device (EVAD) were determined with the pump operating under conditions of 30 and 50 percent systolic duration and a mean flow rate of 5.8 L/min using a flush-mounted hot-film probe. Probe calibrations were performed with the hot-film in two orientations relative to the flow direction: a standard orientation and an orientation in which the hot-film was rotated by 90 deg from the standard orientation. The magnitude and direction of the wall shear stress at each site within the EVAD were estimated from ensemble averaged voltage data recorded for similar standard and rotated film orientations. The results indicate that, during diastole the wall shear stress direction around the pump's periphery for both operating conditions is predominantly perpendicular to the inflow-outflow plane (in the direction of the pusher plate motion) and reaches a peak value of approximately 350 dynes/cm2. The highest wall shear stresses were found near the prosthetic aortic valve (inside the EVAD) under the 30 percent systolic duration condition and are estimated to be as high as 2700 dynes/cm2. Peak shear stress values of 1400 dynes/cm2 were observed in the vicinity of the prosthetic mitral valve under both operating conditions. The results suggested that the valve regions are substantially more hemolytic than other wall regions of the EVAD; the magnitudes of the wall shear stresses are sensitive to operating conditions; and that wall shear in the direction of pusher plate motion can be significant.