Repeated three-dimensional magnetic resonance imaging of atherosclerosis development in innominate arteries of low-density lipoprotein receptor-knockout mice

Background-In vivo methods to evaluate the size and composition of atherosclerotic lesions in animal models of atherosclerosis would assist in the testing of antiatherosclerotic drugs. We have developed an MRI method of detecting atherosclerotic plaque in the major vessels at the base of the heart in low-density lipoprotein (LDL) receptor-knockout (LDLR-/-) mice on a high-fat diet. Methods and Results-Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with approximate to140-mum isotropic resolution, over 30 minutes. Comparison of normal and fat-suppressed images from female LDLR-/- mice I week before and 8 and 12 weeks after the transfer to a high-fat diet allowed visualization and quantification of plaque development in the innominate artery in vivo. Plaque mean cross-sectional area was significantly greater at week 12 in the LDLR-/- mice (0.14+/-0.086 mm(2) [mean+/-SD]) than in wild-type control mice on a normal diet (0.017+/-0.031 mm(2), p

Basal nonselective cation permeability in rat cardiac microvascular endothelial cells

The presence of a basal nonselective cation permeability was mainly investigated in primary cultures of rat cardiac microvascular endothelial cells (CMEC) by applying both the patch-clamp technique and Fura-2 microfluorimetry. With low EGTA in the pipette solution, the resting membrane potential of CMEC was -21.2 +/- 1.1 mV, and a Ca2+-activated Cl- conductance was present. When the intracellular Ca2+ was buffered with high EGTA, the membrane potential decreased to 5.5 +/- 1.2 mV. In this condition, full or partial substitution of external Na+ by NMDG(+) proportionally reduced the inward component of the basal I-V relationship. This current was dependent on extracellular monovalent cations with a permeability sequence of K+ > Cs+ > Na+ > Li+ and was inhibited by Ca2+, La3+, Gd3+, and amiloride. The K+/Na+ permeability ratio, determined using the Goldman-Hodgkin-Katz equation, was 2.01. The outward component of the basal I-V relationship was reduced when intracellular K+ was replaced by NMDG(+), but was not sensitive to substitution by Cs+. Finally, microfluorimetric experiments indicated the existence of a basal Ca2+ entry pathway, inhibited by La3+ and Gd3+. The basal nonselective cation permeability in CMEC could be involved both in the control of myocardial ionic homeostasis, according to the model of the blood-heart barrier, and in the modulation of Ca2+ -dependent processes. (C) 2002 Elsevier Science (USA).

Use of an accelerated chest pain assessment protocol in patients at intermediate risk of adverse cardiac events

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months. Design: Prospective clinical audit. Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features. Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines - 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand. Main outcome measure: Adverse cardiac events during six-month follow-up. Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%). Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography

Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies.

Effect of fatigue on torque output and electromyographic measures of trunk muscles during isometric axial rotation

Objectives: To examine the changes in torque output resulting from fatigue, as well as changes in electromyographic measures of trunk muscles during isometric axial rotation and to compare these changes between directions of axial rotation. Design: Subjects performed fatiguing right and left isometric axial rotation of the trunk at 80% of maximum voluntary contraction while standing upright. Setting: A rehabilitation center. Participants: Twenty-three men with no history of back pain. Interventions: Not applicable. Main Outcome Measures: Surface electromyographic Signals were recorded from 6 trunk muscles bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured. Results: During the fatiguing axial rotation contraction, coupling torques of both sagittal and coronal planes were slightly decreased and no difference was found between directions of axial rotation. Decreasing median frequency and an increase in electromyographic amplitude were also found in trunk muscles with different degrees of changes in individual muscles. There were significant differences (P

Start-up circuit for low-power indoor light energy harvesting applications

A start-up circuit, used in a micro-power indoor light energy harvesting system, is described. This start-up circuit achieves two goals: first, to produce a reset signal, power-on-reset (POR), for the energy harvesting system, and secondly, to temporarily shunt the output of the photovoltaic (PV) cells, to the output node of the system, which is connected to a capacitor. This capacitor is charged to a suitable value, so that a voltage step-up converter starts operating, thus increasing the output voltage to a larger value than the one provided by the PV cells. A prototype of the circuit was manufactured in a 130 nm CMOS technology, occupying an area of only 0.019 mm(2). Experimental results demonstrate the correct operation of the circuit, being able to correctly start-up the system, even when having an input as low as 390 mV using, in this case, an estimated energy of only 5.3 pJ to produce the start-up.

A 5GHz1.8V Low Power CMOS Low-Noise Amplifier

Wireless local-area networks (WLANs) have been deployed as office and home communications infrastructures worldwide. The diversification of the standards, such as IEEE 802.11 series demands the design of RF front-ends. Low power consumption is one of the most important design concerns in the application of those technologies. To maintain competitive hardware costs, CMOS has been used since it is the best solution for low cost and high integration processing, allowing analog circuits to be mixed with digital ones. In the receiver chain, the low noise amplifier (LNA) is one of the most critical blocks in a transceiver design. The sensitivity is mainly determined by the LNA noise figure and gain. It interfaces with the pre-select filter and the mixer. Furthermore, since it is the first gain stage, care must be taken to provide accurate input match, low-noise figure, good linearity and a sufficient gain over a wide band of operation. Several CMOS LNAs have been reported during the last decade, showing that the most research has been done at 802.11/b and GSM standards (900-2400MHz spectrum) and more recently at 802.11/a (5GHz band). One of the more significant disadvantages of 802.11/b is that the frequency band is crowded and subject to interference from other technologies, as is 2.4GHz cordless phones and Bluetooth. As the demand for radio-frequency integrated circuits, operating at higher frequency bands, increases, the IEEE 802.11/a standard becomes a very attractive option to wireless communication system developers. This paper presents the design and implementation of a low power, low noise amplifier aimed at IEEE 802.11a for WLAN applications. It was designed to be integrated with an active balun and mixer, representing the first step toward a fully integrated monolithic WLAN receiver. All the required circuits are integrated at the same die and are powered by 1.8V supply source. Preliminary experimental results (S-parameters) are shown and promise excellent results. The LNA circuit design details are illustrated in Section 2. Spectre simulation results focused at gain, noise figure (NF) and input/output matching are presented in Section 3. Finally, conclusions and comparison with other recently reported LNAs are made in Section 4, followed by future work.

Detection of cardiac biomarker proteins using a disposable based on a molecularly imprinted polymer grafted onto graphite

A low-cost disposable was developed for rapid detection of the protein biomarker myoglobin (Myo) as a model analyte. A screen printed electrode was modified with a molecularly imprinted material grafted on a graphite support and incorporated in a matrix composed of poly(vinyl chloride) and the plasticizer o-nitrophenyloctyl ether. The protein-imprinted material (PIM) was produced by growing a reticulated polymer around a protein template. This is followed by radical polymerization of 4-styrenesulfonic acid, 2-aminoethyl methacrylate hydrochloride, and ethylene glycol dimethacrylate. The polymeric layer was then covalently bound to the graphitic support, and Myo was added during the imprinting stage to act as a template. Non-imprinted control materials (CM) were also prepared by omitting the Myo template. Morphological and structural analysis of PIM and CM by FTIR, Raman, and SEM/EDC microscopies confirmed the modification of the graphite support. The analytical performance of the SPE was assessed by square wave voltammetry. The average limit of detection is 0.79 μg of Myo per mL, and the slope is −0.193 ± 0.006 μA per decade. The SPE-CM cannot detect such low levels of Myo but gives a linear response at above 7.2 μg · mL−1, with a slope of −0.719 ± 0.02 μA per decade. Interference studies with hemoglobin, bovine serum albumin, creatinine, and sodium chloride demonstrated good selectivity for Myo. The method was successfully applied to the determination of Myo urine and is conceived to be a promising tool for screening Myo in point-of-care patients with ischemia.

Protein-responsive polymers for point-of-care detection of cardiac biomarker

This work describes a novel use for the polymeric film, poly(o-aminophenol) (PAP) that was made responsive to a specific protein. This was achieved through templated electropolymerization of aminophenol (AP) in the presence of protein. The procedure involved adsorbing protein on the electrode surface and thereafter electroploymerizing the aminophenol. Proteins embedded at the outer surface of the polymeric film were digested by proteinase K and then washed away thereby creating vacant sites. The capacity of the template film to specifically rebind protein was tested with myoglobin (Myo), a cardiac biomarker for ischemia. The films acted as biomimetic artificial antibodies and were produced on a gold (Au) screen printed electrode (SPE), as a step towards disposable sensors to enable point-of-care applications. Raman spectroscopy was used to follow the surface modification of the Au-SPE. The ability of the material to rebind Myo was measured by electrochemical techniques, namely electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). The devices displayed linear responses to Myo in EIS and SWV assays down to 4.0 and 3.5 μg/mL, respectively, with detection limits of 1.5 and 0.8 μg/mL. Good selectivity was observed in the presence of troponin T (TnT) and creatine kinase (CKMB) in SWV assays, and accurate results were obtained in applications to spiked serum. The sensor described in this work is a potential tool for screening Myo in point-of-care due to the simplicity of fabrication, disposability, short time response, low cost, good sensitivity and selectivity.

Primary cilia and the regulation of hedgehog signaling: link to cardiac development

RESUMO: As células eucarióticas evoluíram um sistema de sinalização complexo que lhes permite responder aos sinais extracelulares e intracelulares. Desta forma, as vias de sinalização são essenciais para a sobrevivência da célula e do organismo, uma vez que regulam processos fundamentais, tais como o desenvolvimento, o crescimento, a imunidade, e a homeostase dos tecidos. A via de transdução de sinal Hedgehog (Hh) envolve o receptor Patched1 (Ptch1), que tem um efeito inibidor sobre a proteína Smoothened (Smo) na ausência dos seus ligandos, as proteínas Sonic hedgehog (Shh). Estas proteínas são reguladores fundamentais do desenvolvimento embrionário, como ilustrado pelas malformações drásticas observadas em embriões humanos e de murganho com perturbações da transdução de sinal da via Hh e que incluem polidactilia, defeitos craniofaciais e malformações ósseas. Igualmente importantes são as consequências da ativação inapropriada da via de sinalização Hh na formação de tumores. Curiosamente, os componentes desta via localizam-se nos cílios primários. Além disso, demonstrou-se que esta localização é crucial para a sinalização através da via Hh. Na presença dos ligandos, Ptch1 é internalizado e destinado a degradação ou sequestrado num compartimento da célula de onde não pode desempenhar o seu papel inibitório. A proteína Arl13b é uma pequena GTPase pertencente à família Arf/Arl da superfamília Ras de pequenas GTPases e foi implicada no síndrome de Joubert, uma ciliopatia caracterizada por ataxia congénita cerebelar, hipotonia, atrso mental e cardiopatia congénita. Murganhos deficientes para Arl13b, chamado hennin (hnn) morrem morrem prematuramente ao dia 13,5 de gestação (E13,5) e exibem anomalias morfológicas nos cílios que levam à interrupção da sinalização Hh. Além disso, a Arl13b está diretamente envolvida na regulação da via Hh, controlando a localização de vários componentes desta via nos cílios primários. Neste trabalho, mostramos que a Arl13b se localiza em circular dorsal ruffles (CDRs), que são estruturas de actina envolvidas em macropinocitose e internalização de recetores, e que regula a sua formação. Além disso, aprofundámos o conhecimento do processo de ativação da via de sinalização Hh, mostrando que as CDRs sequestram seletivamente e internalizam o recetor Ptch1. As CDRs formam-se minutos após ativação da via por ligandos Shh ou pelo agonista de Smo SAG e continuam a ser formadas a partir daí, sugerindo uma indução contínua da reorganização do citoesqueleto de actina quando a via está ativada. Observámos ainda que a inibição da formação de CDRs através do silenciamento de WAVE1, uma proteína necessária para a formação destas estruturas, resulta na diminuição da ativação da via de sinalização Hh. Além disso, o bloqueio da macropinocitose, que se segue ao fecho das CDRs, através do silenciamento de uma proteína necessária para a cisão de macropinossomas, nomeadamente a proteína BARS, tem um efeito semelhante. Estes resultados sugerem que as CDRs e a macropinocitose são necessárias para a ativação da via de sinalização Hh e indicam que esta via de internalização controla os níveis de sinal Hh. Durante o desenvolvimento, as células proliferativas dependem do cílio primário para a transdução de várias vias de sinalização. A via Hh induz a diferenciação do músculo cardíaco. Por conseguinte, os murganhos deficientes na via de sinalização Hh exibem uma variedade de defeitos de lateralidade, incluindo alteração do looping do coração, como pode ser visto em murganhos deficientes para Arl13b. Por conseguinte, investigámos o papel da Arl13b no desenvolvimento do coração. Mostramos que a Arl13b é altamente expressa no coração de embriões de murganho e de murganhos adultos ao nível do mRNA e da proteína. Além disso, o perfil de distribuição da Arl13b no coração segue o dos cílios primários, que são essenciais para o desenvolvimento cardíaco. Corações de murganhos hnn no estadio E12,5 mostram um canal átrio-ventricular aberto, espessamento da camada compacta ventricular e aumento do índice mitótico no ventrículo esquerdo. Além disso, um atraso de 1 a 2 dias no desenvolvimento é observado em corações de murganhos hnn, quando comparados com controlos selvagens no estadio E13,5. Assim, estes resultados sugerem que a Arl13b é necessária para o desenvolvimento embrionário do coração e que defeitos cardíacos podem contribuir para a letalidade embrionária de murganhos hnn. Em suma, foi estabelecido um novo mecanismo para a regulação dos níveis de superfície do recetor Ptch1, que envolve a remodelação do citoesqueleto de actina e a formação de CDRs após a ativação da via de sinalização Hh. Este mecanismo permite um feedback negativo que evita a repressão excessiva da via através da remoção de Ptch1 da superfície da célula. Além disso, determinou-se que uma mutação de perda de função na Arl13b causa defeitos cardíacos durante o desenvolvimento, possivelmente relacionados com a associação dos defeitos em cílios primários e na sinalização Hh, existentes em murganhos deficientes para Arl13b. A via de sinalização Hh tem tido um papel central entre as vias de sinalização, uma vez que a sua regulação é crucial para o funcionamento apropriada da célula. Assim, a descoberta de um novo mecanismo de tráfego através de macropinocitose e CDRs que controla a ativação e repressão da via de sinalização Hh traz novas perspetivas de como esta via pode ser regulada e pode ainda conduzir à identificação de novos alvos e estratégias terapêuticas. --------------------ABSTRACT: Eukaryotic cells have evolved a complex signaling system that allows them to respond to extracellular and intracellular cues. Signaling pathways are essential for cell and organism survival, since they regulate fundamental processes such as development, growth, immunity, and tissue homeostasis. The Hedgehog (Hh) pathway of signal transduction involves the receptor Patched1 (Ptch1), which has an inhibitory effect on Smoothened (Smo) in the absence of its ligands, the Sonic hedgehog (Shh) proteins. These proteins are fundamental regulators of embryonic development, as illustrated by the dramatic malformations seen in human and mouse embryos with perturbed Hh signal transduction that include polydactyly, craniofacial defects and skeletal malformations. Equally important are the consequences of inappropriate activation of the Hh signaling response in tumor formation. Interestingly, the components of this pathway localize to primary cilia. Moreover, it has been shown that this localization is crucial for Hh signaling. However, in the presence of the ligands, Ptch1 is internalized and destined for degradation or sequestered in a cell compartment where it no longer can play its inhibitory role. ADP-ribosylation factor-like (Arl) 13b, a small GTPase belonging to Arf/Arl family of the Ras superfamily of small GTPases has been implicated in Joubert syndrome, a ciliopathy characterized by congenital cerebellar ataxia, hypotonia, intellectual disability and congenital heart disease. Arl13b-deficient mice, called hennin (hnn) die at embryonic day 13.5 (E13.5) and display morphological abnormalities in primary cilia that lead to the disruption of Hh signaling. Furthermore, Arl13b is directly involved in the regulation of Hh signaling by controlling the localization of several components of this pathway to primary cilia. Here, we show that Arl13b localizes to and regulates the formation of circular dorsal rufles (CDRs), which are actin-basedstructures known to be involved in macropinocytosis and receptor internalization. Additionally, we extended the knowledge of the Hh signaling activation process by showing that CDRs selectively sequester and internalize Ptch1 receptors. CDRs are formed minutes after Hh activation by Shh ligands or the Smo agonist SAG and keep being formed thereafter, suggesting a continuous induction of actin reorganization when the pathway is switched on. Importantly, we observed that disruption of CDRs by silencing WAVE1, a protein required for CDR formation, results in down-regulation of Hh signaling activation. Moreover, the blockade of macropinocytosis, which follows CDR closure, through silencing of a protein necessary for the fission of macropinosomes, namely BARS has a similar effect. These results suggest that CDRs and macropinocytosis are necessary for activation of Hh signaling and indicate that this pathway of internalization controls Hh signal levels. During development, proliferating cells rely on the primary cilium for the transduction of several signaling pathways. Hh induces the differentiation of cardiac muscle. Accordingly, Hh-deficient mice display a variety of laterality defects, including alteration of heart looping, as seen in Arl13b-deficient mice. Therefore, we investigated the role of Arl13b in heart development. We show that Arl13b is highly expressed in the heart of both embryonic and adult mice at mRNA and protein levels. Also, Arl13b localization profile mimics that of primary cilia, which have been shown to be essential to early heart development. E12.5 hnn hearts show an open atrioventricular channel, increased thickening of the ventricular compact layer and increased mitotic index in the left ventricle. Moreover, a delay of 1 to 2 days in development is observed in hnn hearts, when compared to wild-type controls at E13.5. Hence, these results suggest that Arl13b is necessary for embryonic heart development and that cardiac defects might contribute to the embryonic lethality of hnn mice. Altogether, we established a novel mechanism for the regulation of Ptch1 surface levels, involving cytoskeleton remodeling and CDR formation upon Hh signaling activation. This mechanism allows a negative feedback loop that prevents excessive repression of the pathway by removing Ptch1 from the cell surface. Additionally, we determined that the Arl13b loss-offunction mutation causes cardiac defects during development, possibly related to the associated ciliary and Hh signaling defects found in Arl13b-deficient mice. Hh signaling has taken a center stage among the signaling pathways since its regulation is crucial for the appropriate output and function of the cell. Hence, the finding of a novel trafficking mechanism through CDRs and macropinocytosis that controls Hh signaling activation and repression brings new insights to how this pathway can be regulated and can lead to the discovery of novel therapeutic targets and strategies.

Invasive hemodynamic monitoring in the postoperative period of cardiac surgery

OBJETIVE: To assess the hemodynamic profile of cardiac surgery patients with circulatory instability in the early postoperative period (POP). METHODS: Over a two-year period, 306 patients underwent cardiac surgery. Thirty had hemodynamic instability in the early POP and were monitored with the Swan-Ganz catheter. The following parameters were evaluated: cardiac index (CI), systemic and pulmonary vascular resistance, pulmonary shunt, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), oxygen delivery and consumption, use of vasoactive drugs and of circulatory support. RESULTS: Twenty patients had low cardiac index (CI), and 10 had normal or high CI. Systemic vascular resistance was decreased in 11 patients. There was no correlation between oxygen delivery (DO2) and consumption (VO2), p=0.42, and no correlation between CVP and PCWP, p=0.065. Pulmonary vascular resistance was decreased in 15 patients and the pulmonary shunt was increased in 19. Two patients with CI < 2L/min/m² received circulatory support. CONCLUSION: Patients in the POP of cardiac surgery frequently have a mixed shock due to the systemic inflammatory response syndrome (SIRS). Therefore, invasive hemodynamic monitoring is useful in handling blood volume, choice of vasoactive drugs, and indication for circulatory support.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

Predictors of Conversion from Radial Into Femoral Access in Cardiac Catheterization

Background: Fewer bleeding complications and early ambulation make radial access a privileged route for cardiac catheterization. However, transradial (TR) approach is not always successful, requiring its conversion into femoral access. Objectives: To evaluate the rate of conversion from radial into femoral access in cardiac catheterization and to identify its predictors. Methods: Prospective dual-center registry, including 7632 consecutive patients undergoing catheterization via the radial access between Jan/2009 and Oct/2012. We evaluated the incidence of conversion into femoral access and its predictors by logistic regression analysis. Results: The patients’ mean age was 66 ± 11 years, and 32% were women. A total of 2969 procedures (38.4%) were percutaneous coronary interventions (PCI), and the most used first intention arterial access was the right radial artery (97.6%). Radial access failure rate was 5.8%. Independent predictors of conversion from radial into femoral access were the use of short introducer sheaths (OR 3.047, CI: 2.380-3.902; p < 0.001), PCI (OR 1.729, CI: 1.375-2.173; p < 0.001), female sex (OR 1.569, CI: 1.234-1.996; p < 0.001), multivessel disease (OR 1.457, CI: 1.167-1.819; p = 0.001), body surface area (BSA) ≤ 1.938 (OR 1.448, CI: 1.120-1.871; p = 0.005) and age > 66 years (OR 1.354, CI: 1.088-1.684; p = 0.007). Conclusion: Transradial approach for cardiac catheterization has a high success rate and the need for its conversion into femoral access in this cohort was low. Female sex, older age, smaller BSA, the use of short introducer sheaths, multivessel disease and PCI were independent predictors of conversion into femoral access.

Myocardial Scintigraphy in the Evaluation of Cardiac Events in Patients without Typical Symptoms

AbstractBackground:Cardiovascular disease is a leading cause of death in the world and in Brazil. Myocardial scintigraphy is an important noninvasive method for detecting ischemia in symptomatic patients, but its use in asymptomatic ones or those with atypical symptoms is yet to be defined.Objective:To verify the presence of major cardiac events in asymptomatic patients or those with atypical symptoms (atypical chest pain or dyspnea) that underwent myocardial scintigraphy (MS), over a period of 8 years. Secondary objectives were to identify cardiac risk factors associated with myocardial scintigraphy abnormalities and possible predictors for major cardiac events in this group.Methods:This was a retrospective, observational study using the medical records of 892 patients that underwent myocardial scintigraphy between 2005 and 2011 and who were followed until 2013 for assessment of major cardiac events and risk factors associated with myocardial scintigraphy abnormalities. Statistical analysis was performed by Fisher’s exact test, logistic regression and Kaplan-Meyer survival curves, with statistical significance being set at p ≤ 0.05.Results:Of the total sample, 52.1% were men, 86.9% were hypertensive, 72.4% had hyperlipidemia, 33.6% were diabetic, and 12.2% were smokers; 44.5% had known coronary artery disease; and 70% had high Framingham score, 21.8% had moderate and 8% had low risk. Of the myocardial scintigraphies, 58.6% were normal, 26.1% suggestive of fibrosis and 15.3% suggestive of ischemia. At evolution, 13 patients (1.5%) had non-fatal myocardial infarction and six individuals (0.7%) died. The group with normal myocardial scintigraphy showed longer period of time free of major cardiac events, non-fatal myocardial infarction (p = 0.036) and death. Fibrosis in the myocardial scintigraphy determined a 2.4-fold increased risk of non-fatal myocardial infarction and five-fold higher risk of death (odds ratio: 2.4 and 5.7, respectively; p = 0.043).Conclusion:The occurrence of major cardiac events in 8 years was small. Patients with fibrosis at MS had more major events, whereas patients with normal MS result had fewer major cardiac events, with higher survival.

Cardiac Surgery Costs According to the Preoperative Risk in the Brazilian Public Health System

AbstractBackground:Heart surgery has developed with increasing patient complexity.Objective:To assess the use of resources and real costs stratified by risk factors of patients submitted to surgical cardiac procedures and to compare them with the values reimbursed by the Brazilian Unified Health System (SUS).Method:All cardiac surgery procedures performed between January and July 2013 in a tertiary referral center were analyzed. Demographic and clinical data allowed the calculation of the value reimbursed by the Brazilian SUS. Patients were stratified as low, intermediate and high-risk categories according to the EuroSCORE. Clinical outcomes, use of resources and costs (real costs versus SUS) were compared between established risk groups.Results:Postoperative mortality rates of low, intermediate and high-risk EuroSCORE risk strata showed a significant linear positive correlation (EuroSCORE: 3.8%, 10%, and 25%; p < 0.0001), as well as occurrence of any postoperative complication EuroSCORE: 13.7%, 20.7%, and 30.8%, respectively; p = 0.006). Accordingly, length-of-stay increased from 20.9 days to 24.8 and 29.2 days (p < 0.001). The real cost was parallel to increased resource use according to EuroSCORE risk strata (R$ 27.116,00 ± R$ 13.928,00 versus R$ 34.854,00 ± R$ 27.814,00 versus R$ 43.234,00 ± R$ 26.009,00, respectively; p < 0.001). SUS reimbursement also increased (R$ 14.306,00 ± R$ 4.571,00 versus R$ 16.217,00 ± R$ 7.298,00 versus R$ 19.548,00 ± R$935,00; p < 0.001). However, as the EuroSCORE increased, there was significant difference (p < 0.0001) between the real cost increasing slope and the SUS reimbursement elevation per EuroSCORE risk strata.Conclusion:Higher EuroSCORE was related to higher postoperative mortality, complications, length of stay, and costs. Although SUS reimbursement increased according to risk, it was not proportional to real costs.