Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry

BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.

Comparative efficacy of 2 topical anesthetics for the placement of orthodontic temporary anchorage devices.

This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P < .05) and success rate (P < .01) between drugs were seen, but no significant difference in pulse rate change between the topical anesthetics was observed (P > .05). It was concluded that when the efficacy of topical benzocaine and of a combination product was compared as the sole anesthetic to facilitate acceptable pain control for placement of orthodontic temporary anchorage devices, the combination product was considerably more efficacious.

Physiologic and hematologic concerns of rotary blood pumps: what needs to be improved?

Over the past few decades, advances in ventricular assist device (VAD) technology have provided a promising therapeutic strategy to treat heart failure patients. Despite the improved performance and encouraging clinical outcomes of the new generation of VADs based on rotary blood pumps (RBPs), their physiologic and hematologic effects are controversial. Currently, clinically available RBPs run at constant speed, which results in limited control over cardiac workload and introduces blood flow with reduced pulsatility into the circulation. In this review, we first provide an update on the new challenges of mechanical circulatory support using rotary pumps including blood trauma, increased non-surgical bleeding rate, limited cardiac unloading, vascular malformations, end-organ function, and aortic valve insufficiency. Since the non-physiologic flow characteristic of these devices is one of the main subjects of scientific debate in the literature, we next emphasize the latest research regarding the development of a pulsatile RBP. Finally, we offer an outlook for future research in the field.

Effects of Thoratec pulsatile ventricular assist device (PVAD) timing on the abdominal aortic wave intensity pattern

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculo-aortic cannulation. The start of PVAD ejection was synchronized to the native R-wave and delayed between 0 % - 90 % of the cardiac cycle in 10 % steps or phase shifts (PS). Pressure and velocity signals were registered, using a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe, that non-invasive WIA could potentially be used clinically to assess the mechanical load of the LV, and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.

Transcranial Doppler-guided deairing of a pediatric ventricular assist device: experience with twins

We report the intraoperative courses of 2 consecutive Berlin Heart Excor® Pediatric Ventricular Assist Device implantations, in which transcranial Doppler ultrasonography helped to detect macroscopically undetected residual air bubbles captured in the pump after air removal had been correctly performed according to manufacturer's specifications. Our experience with these cases suggests that a beat-to beat deairing maneuver guided by transcranial Doppler is a useful strategy for reducing cerebral exposure to perioperative gaseous microembolism.

The association between maternal use of spermicides, condoms, intra-uterine devices or progesterone and major structural birth defects

Birth defects occur in 1 of every 33 babies born in the United States, and are the leading cause of infant death. Mothers using contraceptives that become pregnant may continue to use their contraceptives after their first missed menstrual period, thus exposing their baby in utero to the contraceptive product. Progesterone is also sometimes prescribed during the first trimester of pregnancy to mothers with a history of miscarriages or infertility problems. To ensure the safety of these products, it is important to investigate whether there is an increased occurrence of babies born with birth defects to mothers using various contraceptive methods or progesterone in early pregnancy. Using data from the National Birth Defects Prevention Study (NBDPS), an ongoing multi-state, population based case-control study, this study assessed maternal exposures to IUDs, spermicides, condoms and progesterone in early pregnancy. ^ Progesterone used for threatened miscarriage during the first three months of pregnancy was associated with an increased occurrence of hypoplastic left heart (adjusted odds ratios (OR) 2.24, 95% CI 1.13-4.21), perimembranous ventricular septal defects (OR 1.64, 95% CI 1.10-2.41), septal associations (OR 2.52, 95% CI 1.45-4.24), esophageal atresia (OR 1.82, 95% CI 1.04-3.08), and hypospadias (OR 2.12, 95% CI 1.41-3.18). Mothers using progesterone for injectable contraception had increased (OR > 2.5), but insignificant odds ratios for anencephaly, septal associations, small intestinal atresias and omphalocel. Progesterone used for fertility was not associated with an increased occurrence of any birth defects examined. ^ Mothers using progesterone for fertility assistance and threatened miscarriage were very similar with respect to their demographics and pregnancy history. They also both reported similar types of progesterone. Thus, if progesterone was a causal risk factor for birth defects we would have expected to observe similar increases in risk among mothers using progesterone for both indications. Because we predominantly observed increased associations among mothers using progesterone for threatened miscarriage but not fertility assistance, it is possible the increased associations we observed were confounded by indication (i.e. progesterone was administered for vaginal bleeding which occurred as a sequelae to the formation of a congenital anomaly. ^ No significant increased associations were observed between maternal spermicide use during pregnancy and 26 of 27 types of structural malformations. While multiple statistical tests were performed we observed first trimester maternal spermicide use to be associated with a significant increased occurrence of perimembranous ventricular septal defects (OR 2.21, 95% CI 1.16-4.21). A decreased occurrence (OR < 1.0) was observed for several categories of birth defects among mothers who conceived in the first cycle after discontinuing the use of spermicides (22 of 28) or male condoms (23 of 33). ^ Overall the percent of IUD use was similar between mothers of controls and mothers of all cases in aggregate (crude OR 1.05, 95% CI 0.61-1.84). Power was limited to detect significant associations between IUD use and birth defects, however mothers using an IUD in the month immediately prior to conception or during pregnancy were not associated with an increase of birth defects. Limb defects and amniotic band sequence previously reported to be associated with IUD use during pregnancy were not found to occur among any mothers reporting the use of an IUD during pregnancy.^

Heart Failure Monitoring System Based on Wearable and Information Technologies

In Europe, Cardiovascular Diseases (CVD) are the leading source of death, causing 45% of all deceases. Besides, Heart Failure, the paradigm of CVD, mainly affects people older than 65. In the current aging society, the European MyHeart Project was created, whose mission is to empower citizens to fight CVD by leading a preventive lifestyle and being able to be diagnosed at an early stage. This paper presents the development of a Heart Failure Management System, based on daily monitoring of Vital Body Signals, with wearable and mobile technologies, for the continuous assessment of this chronic disease. The System makes use of the latest technologies for monitoring heart condition, both with wearable garments (e.g. for measuring ECG and Respiration); and portable devices (such as Weight Scale and Blood Pressure Cuff) both with Bluetooth capabilities

Contribution towards intelligent service management in wearable and ubiquitous devices

Hoy en día asistimos a un creciente interés por parte de la sociedad hacia el cuidado de la salud. Esta afirmación viene apoyada por dos realidades. Por una parte, el aumento de las prácticas saludables (actividad deportiva, cuidado de la alimentación, etc.). De igual manera, el auge de los dispositivos inteligentes (relojes, móviles o pulseras) capaces de medir distintos parámetros físicos como el pulso cardíaco, el ritmo respiratorio, la distancia recorrida, las calorías consumidas, etc. Combinando ambos factores (interés por el estado de salud y disponibilidad comercial de dispositivos inteligentes) están surgiendo multitud de aplicaciones capaces no solo de controlar el estado actual de salud, también de recomendar al usuario cambios de hábitos que lleven hacia una mejora en su condición física. En este contexto, los llamados dispositivos llevables (weareables) unidos al paradigma de Internet de las cosas (IoT, del inglés Internet of Things) permiten la aparición de nuevos nichos de mercado para aplicaciones que no solo se centran en la mejora de la condición física, ya que van más allá proponiendo soluciones para el cuidado de pacientes enfermos, la vigilancia de niños o ancianos, la defensa y la seguridad, la monitorización de agentes de riesgo (como bomberos o policías) y un largo etcétera de aplicaciones por llegar. El paradigma de IoT se puede desarrollar basándose en las existentes redes de sensores inalámbricos (WSN, del inglés Wireless Sensor Network). La conexión de los ya mencionados dispositivos llevables a estas redes puede facilitar la transición de nuevos usuarios hacia aplicaciones IoT. Pero uno de los problemas intrínsecos a estas redes es su heterogeneidad. En efecto, existen multitud de sistemas operativos, protocolos de comunicación, plataformas de desarrollo, soluciones propietarias, etc. El principal objetivo de esta tesis es realizar aportaciones significativas para solucionar no solo el problema de la heterogeneidad, sino también de dotar de mecanismos de seguridad suficientes para salvaguardad la integridad de los datos intercambiados en este tipo de aplicaciones. Algo de suma importancia ya que los datos médicos y biométricos de los usuarios están protegidos por leyes nacionales y comunitarias. Para lograr dichos objetivos, se comenzó con la realización de un completo estudio del estado del arte en tecnologías relacionadas con el marco de investigación (plataformas y estándares para WSNs e IoT, plataformas de implementación distribuidas, dispositivos llevables y sistemas operativos y lenguajes de programación). Este estudio sirvió para tomar decisiones de diseño fundamentadas en las tres contribuciones principales de esta tesis: un bus de servicios para dispositivos llevables (WDSB, Wearable Device Service Bus) basado en tecnologías ya existentes tales como ESB, WWBAN, WSN e IoT); un protocolo de comunicaciones inter-dominio para dispositivos llevables (WIDP, Wearable Inter-Domain communication Protocol) que integra en una misma solución protocolos capaces de ser implementados en dispositivos de bajas capacidades (como lo son los dispositivos llevables y los que forman parte de WSNs); y finalmente, la tercera contribución relevante es una propuesta de seguridad para WSN basada en la aplicación de dominios de confianza. Aunque las contribuciones aquí recogidas son de aplicación genérica, para su validación se utilizó un escenario concreto de aplicación: una solución para control de parámetros físicos en entornos deportivos, desarrollada dentro del proyecto europeo de investigación “LifeWear”. En este escenario se desplegaron todos los elementos necesarios para validar las contribuciones principales de esta tesis y, además, se realizó una aplicación para dispositivos móviles por parte de uno de los socios del proyecto (lo que contribuyó con una validación externa de la solución). En este escenario se usaron dispositivos llevables tales como un reloj inteligente, un teléfono móvil con sistema operativo Android y un medidor del ritmo cardíaco inalámbrico capaz de obtener distintos parámetros fisiológicos del deportista. Sobre este escenario se realizaron diversas pruebas de validación mediante las cuales se obtuvieron resultados satisfactorios. ABSTRACT Nowadays, society is shifting towards a growing interest and concern on health care. This phenomenon can be acknowledged by two facts: first, the increasing number of people practising some kind of healthy activity (sports, balanced diet, etc.). Secondly, the growing number of commercial wearable smart devices (smartwatches or bands) able to measure physiological parameters such as heart rate, breathing rate, distance or consumed calories. A large number of applications combining both facts are appearing. These applications are not only able to monitor the health status of the user, but also to provide recommendations about routines in order to improve the mentioned health status. In this context, wearable devices merged with the Internet of Things (IoT) paradigm enable the proliferation of new market segments for these health wearablebased applications. Furthermore, these applications can provide solutions for the elderly or baby care, in-hospital or in-home patient monitoring, security and defence fields or an unforeseen number of future applications. The introduced IoT paradigm can be developed with the usage of existing Wireless Sensor Networks (WSNs) by connecting the novel wearable devices to them. In this way, the migration of new users and actors to the IoT environment will be eased. However, a major issue appears in this environment: heterogeneity. In fact, there is a large number of operating systems, hardware platforms, communication and application protocols or programming languages, each of them with unique features. The main objective of this thesis is defining and implementing a solution for the intelligent service management in wearable and ubiquitous devices so as to solve the heterogeneity issues that are presented when dealing with interoperability and interconnectivity of devices and software of different nature. Additionally, a security schema based on trust domains is proposed as a solution to the privacy problems arising when private data (e.g., biomedical parameters or user identification) is broadcasted in a wireless network. The proposal has been made after a comprehensive state-of-the-art analysis, and includes the design of a Wearable Device Service Bus (WDSB) including the technologies collected in the requirement analysis (ESB, WWBAN, WSN and IoT). Applications are able to access the WSN services regardless of the platform and operating system where they are running. Besides, this proposal also includes the design of a Wearable Inter-Domain communication Protocols set (WIDP) which integrates lightweight protocols suitable to be used in low-capacities devices (REST, JSON, AMQP, CoAP, etc...). Furthermore, a security solution for service management based on a trustworthy domains model to deploy security services in WSNs has been designed. Although the proposal is a generic framework for applications based on services provided by wearable devices, an application scenario for testing purposes has been included. In this validation scenario it has been presented an autonomous physical condition performance system, based on a WSN, bringing the possibility to include several elements in an IoT scenario: a smartwatch, a physiological monitoring device and a smartphone. In summary, the general objective of this thesis is solving the heterogeneity and security challenges arising when developing applications for WSNs and wearable devices. As it has been presented in the thesis, the solution proposed has been successfully validated in a real scenario and the obtained results were satisfactory.

Calix[6]arene Derivatives as Pivotal Components of Working Devices and Molecular Machine Prototypes

This Ph.D. thesis describes the synthesis, characterization and study of calix[6]arene derivatives as pivotal components for the construction of molecular machine prototypes. Initially, the ability of a calix[6]arene wheel to supramolecularly assist and increase the rate of a nucleophilic substitution reaction was exploited for the synthesis of two constitutionally isomeric oriented rotaxanes. Then, the synthesis and characterization of several hetero-functionalised calix[6]arene derivatives and the possibility to obtain molecular muscle prototypes was reported. The ability of calix[6]arenes to form oriented pseudorotaxane towards dialkyl viologen axles was then exploited for the synthesis of two calixarene-based [2]catenanes. As last part of this thesis, studies on the electrochemical response of the threading-dethreading process of calix[6]arene-based pseudorotaxanes and rotaxanes supported on glassy carbon electrodes are reported.

Towards Batteryless Cardiac Implantable Electronic Devices – The Swiss Way

Energy harvesting devices are widely discussed as an alternative power source for todays active implantable medical devices. Repeated battery replacement procedures can be avoided by extending the implants life span, which is the goal of energy harvesting concepts. This reduces the risk of complications for the patient and may even reduce device size. The continuous and powerful contractions of a human heart ideally qualify as a battery substitute. In particular, devices in close proximity to the heart such as pacemakers, defibrillators or bio signal (ECG) recorders would benefit from this alternative energy source. The clockwork of an automatic wristwatch was used to transform the hearts kinetic energy into electrical energy. In order to qualify as a continuous energy supply for the consuming device, the mechanism needs to demonstrate its harvesting capability under various conditions. Several in-vivo recorded heart motions were used as input of a mathematical model to optimize the clockworks original conversion efficiency with respect to myocardial contractions. The resulting design was implemented and tested during in-vitro and in-vivo experiments, which demonstrated the superior sensitivity of the new design for all tested heart motions.

Magnetic Devices and Techniques for the Study of Viscoelasticity of Biomaterials and Myocardial Forces

Thesis (Ph.D.)--University of Washington, 2016-06

The effect of innate compliance on the performance of a counterpulsation device

Cardiovascular disease (CVD) continues to be one of the top causes of mortality in the world. World Heart Organization (WHO) reported that in 2004, CVD contributed to almost 30% of death from estimated worldwide death figures of 58 million[1]. Heart failure treatment varies from lifestyle adjustment to heart transplantation; its aims are to reduce HF symptoms, prolong patient survival and minimize risk [2]. One alternative available in the market for HF treatment is Left Ventricular Assist Device (LVAD). Chronic Intermittent Mechanical Support (CIMS) device is a novel (LVAD) heart failure treatment using counterpulsation similar to Intra Aortic Balloon Pumps (IABP). However, the implantation site of the CIMS balloon is in the ascending aorta just distal to aortic valve contrasted with IABP in the descending aorta. Counterpulsation coupled with implantation close to the aortic valve enables comparable flow augmentation with reduced balloon volume. Two prototypes of the CIMS balloon were constructed using rapid prototyping: the straight-body model is a cylindrical tube with a silicone membrane lining with zero expansive compliance. The compliant-body model had a bulging structure that allowed the membrane to expand under native systolic pressure increasing the device’s static compliance to 1.5 mL/mmHg. This study examined the effect of device compliance and vascular compliance on counterpulsating flow augmentation. Both prototypes were tested on a two-element Windkessel model human mock circulatory loop (MCL). The devices were placed just distal to aortic valve and left coronary artery. The MCL mimicked HF with cardiac output of 3 L/min, left ventricular pressure of 85/15 mmHg, aortic pressure of 70/50 mmHg and left coronary artery flow rate of 66 mL/min. The mean arterial pressure (MAP) was calculated to be 57 mmHg. Arterial compliance was set to be1.25 mL/mmHg and 2.5 mL/mmHg. Inflation of the balloon was triggered at the dicrotic notch while deflation was at minimum aortic pressure prior to systole. Important haemodynamics parameters such as left ventricular pressure (LVP), aortic pressure (AoP), cardiac output (CO), left coronary artery flowrate (QcorMean), and dP (Peak aortic diastolic augmentation pressure – AoPmax ) were simultaneously recorded for both non-assisted mode and assisted mode. ANOVA was used to analyse the effect of both factors (balloon and arterial compliance) to flow augmentation. The results showed that for cardiac output and left coronary artery flowrate, there were significant difference between balloon and arterial compliance at p < 0.001. Cardiac output recorded maximum output at 18% for compliant body and stiff arterial compliance. Left coronary artery flowrate also recorded around 20% increase due to compliant body and stiffer arterial compliance. Resistance to blood ejection recorded highest difference for combination of straight body and stiffer arterial compliance. From these results it is clear that both balloon and arterial compliance are statistically significant factors for flow augmentation on peripheral artery and reduction of resistance. Although the result for resistance reduction was different from flow augmentation, these results serves as an important aspect which will influence the future design of the CIMS balloon and its control strategy. References: 1. Mathers C, Boerma T, Fat DM. The Global Burden of disease:2004 update. Geneva: World Heatlh Organization; 2008. 2. Jessup M, Brozena S. Heart Failure. N Engl J Med 2003;348:2007-18.

The application of laser welding on Left Ventricular Assist Device (LVAD)

A successful and useful treatment for end-stage heart failure is Left ventricular assist device (LVAD). An important part - a hydrodynamically suspended impeller exposed to corrosive conditions, required to sealed hermetically into micro packages. Laser beam welded (LBW) Ti6Al4V alloy has been adopted in anti-corrosion micro packages for the impeller of a (LVAD). Thin and narrow welds were required for such medical equipment. Pulsed Nd:YAG welding was successfully adopted as sealing method for the impeller. ©2011 IEEE.