Abnormal Iron Status and Adverse Outcome After Elective Cardiac Surgery: A Prospective, Observational Multicenter Study.

OBJECTIVES: To investigate the incidence of preoperative abnormal iron status and its association with packed red blood cell (PRBC) transfusion, postoperative major complications, and new onset of clinically significant disability in patients undergoing elective cardiac surgery. DESIGN: A prospective, observational multicenter cohort study. SETTING: Three cardiac surgical centers in the Netherlands between 2019 and 2021. Recruitment was on hold between March and May 2020 due to COVID-19. PATIENTS: A total of 427 patients aged 60 years and older who underwent elective on-pump cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a 30-day PRBC transfusion. Secondary endpoints were postoperative major complications within 30 days (eg, acute kidney injury, sepsis), and new onset of clinically significant disability within 120 days of surgery. Iron status was evaluated before surgery. Abnormal iron status was present in 45.2% of patients (n = 193), and most frequently the result of iron deficiency (27.4%, n = 117). An abnormal iron status was not associated with PRBC transfusion (adjusted relative risk [ARR] 1.2; 95% CI 0.9-1.8: p = 0.227) or new onset of clinically significant disability (ARR 2.0; 95% CI 0.9-4.6: p = 0.098). However, the risk of postoperative major complications was increased in patients with an abnormal iron status (ARR 1.7; 95% CI 1.1-2.5: p = 0.012). CONCLUSIONS: An abnormal iron status before elective cardiac surgery was associated with an increased risk of postoperative major complications but not with PRBC transfusion or a new onset of clinically significant disability.

Cardiac Surgery in Jehovah's Witnesses: 329 Consecutive Cases.

OBJECTIVES: This study aimed to describe the outcome of Jehovah's Witnesses (JWs) undergoing cardiac surgery at the authors' center. DESIGN: A single-center retrospective cohort study. SETTING: At a cardiovascular center with a tertiary intensive care unit (ICU) and specific experience with cardiac surgery in JWs. The institutional protocol describing all perioperative care in JWs has been applied for 21 years. PARTICIPANTS: All JWs undergoing cardiac surgery in the Amphia Hospital from January 1, 2001 to January 31, 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study cohort comprised 329 JWs undergoing cardiac surgery. Twenty-three patients (6.8%) were treated preoperatively for anemia. The mean European System for Cardiac Operative Risk Evaluation score was 5.1 (range 0-18). Coronary artery bypass grafting (53.2%) was performed most frequently, followed by aortic valve replacement (13.4%). Mean preoperative hemoglobin levels were 14.5 g/dL (range 9.8-18.5 g/dL), dropping to 11.6 g/dL (range 6.6-15.6 g/dL) at hospital discharge. Mean blood loss was 439 ± 349 mL in the first 12 hours postsurgery. Maximum mean postoperative troponin levels were 431 ± 424 ng/L. Resternotomy and postoperative myocardial infarction occurred in 3.6% and 4.2% of patients, respectively. On average, patients had an ICU stay of 1.4 ± 1.8 days and a hospital stay of 6.8 ± 4.2 days. Hospital mortality was 0.6% and was related to cardiac failure. CONCLUSIONS: This study demonstrated that cardiac surgery in JWs is safe when adhering to a strict perioperative patient blood management protocol.

Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis.

BACKGROUND: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. METHODS: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. RESULTS: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4-1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3-1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4-2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. CONCLUSIONS: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes.

Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial.

AIMS: Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesized that preoperative administration of the glucagon-like peptide-1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. MATERIALS AND METHODS: In this randomized, blinded, placebo-controlled, parallel-group, balanced (1:1), multicentre randomized, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomized to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus algorithm. The primary outcome was insulin administration for blood glucose >8.0 mmol/L in the operating theatre. Research pharmacists used centralized, stratified, variable-block, randomization software. Patients, care providers and study personnel were blinded to treatment allocation. RESULTS: Between June 2017 and August 2018, 278 patients were randomized to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group, 55 (43%) patients required additional insulin compared with 80 (61%) in the placebo group and absolute difference 18% (95% confidence interval 5.9-30.0, P = 0.003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality or postoperative complications. CONCLUSIONS: Preoperative liraglutide, compared with placebo, reduces insulin requirements while improving perioperative glycaemic control during cardiac surgery.

Measures to Prevent Neurologic Deficits in Urgent CABG Surgery With Bilateral Carotid Occlusion.

Patients with bilateral high-degree carotid stenosis or occlusion impose high risk for neurologic complications during coronary artery bypass graft surgery (CABG). Former articles have described successful CABG in patients with bilateral carotid artery occlusion with uneventful recovery, with perioperative cerebral blood flow monitoring consisting of electroencephalography or near-infrared spectroscopy. In this case report, we describe the use of pulsatile flow on cardiopulmonary bypass and transcranial Doppler monitoring during successful CABG in a patient with bilateral carotid occlusion, leading to a safe approach where changes in cerebral blood flow were seen and analyzed with no lag between event and monitoring.

Intraoperative glycemic control without insulin infusion during pediatric cardiac surgery for congenital heart disease.

BACKGROUND: Many studies are reporting that the occurrence of hyperglycemia in the postoperative period is associated with increased morbidity and mortality rates in children after cardiac surgery for congenital heart disease. This study sought to determine blood glucose levels in standard pediatric cardiac anesthesiological management without insulin infusions. METHODS: The study population consisted of 204 consecutive pediatric patients aged from 3 days to 15.4 years undergoing open cardiac surgery for congenital heart disease between June 2007 and January 2009. Glucose-containing fluids were not administrated intraoperatively, and all patients received high dose of opioids (sufentanil 10 mcg·kg(-1) ) and steroids (30 mg·kg(-1) methylprednisolone) iv. Glucose levels were measured before CPB, 10 min after initiation of CPB, every hour on CPB, post-CPB, and on arrival at intensive care unit (ICU). RESULTS: Intraoperatively, only one patient had a glucose level <50 mg·dl(-1) (=34.2 mg·dl(-1) ), 57/204 patients (27.9%) had at least one intraoperative glucose >180 mg·dl(-1) , but only 12 patients (5.8%) had a glucose level >180 mg·dl(-1) at ICU arrival. Thirty-day mortality was 1.5% (3/204). Younger age, lower body weight, and lower CPB temperature were associated with hyperglycemia at ICU arrival, as were higher RACHS and Aristotle severity scores. CONCLUSION: A conventional (no insulin, no glucose) anesthetic management seems sufficient in the vast majority of patients (96.5%). Special attention should be paid to small neonates with complex congenital heart surgery, in whom insulin treatment may be contemplated.

A 0.6-protamine/heparin ratio in cardiac surgery is associated with decreased transfusion of blood products.

OBJECTIVES: In cardiac surgery, adequate heparinization is necessary to prevent thrombus formation in the cardiopulmonary bypass (CPB). To counteract the heparin effect after weaning from CPB, protamine is administered. The optimal protamine/heparin ratio is still unknown. METHODS: In this before-after study, we evaluated the effect of a 0.6/1-protamine/heparin ratio implementation as of May 2017 versus a 0.8/1-protamine/heparin ratio on the 12-h postoperative blood loss and the amount of blood and blood component transfusions (fresh frozen plasma, packed red blood cells, fibrinogen concentrate, platelet concentrate and prothrombin complex concentrate) after cardiac surgery. A total of 2051 patients who underwent cardiac surgery requiring CPB between May 2016 and May 2018 were included. RESULTS: In the 0.6/1-protamine/heparin ratio group, only 28.8% of the patients received blood component transfusion, compared to 37.9% of the patients in the 0.8/1-ratio group (P < 0.001). The median 12-h postoperative blood loss was 230 ml (interquartile range 140-320) in the 0.6/1-ratio group versus 260 ml (interquartile range 155-365) in the 0.8/1-ratio group (P < 0.001). CONCLUSIONS: A 0.6/1-protamine/heparin ratio after weaning from CPB is associated with a significantly reduced 12-h postoperative blood loss and blood components transfusion.

Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial.

INTRODUCTION: Previous studies demonstrated the cardioprotective properties of glucagon-like peptide-1 receptor agonists in patients with diabetes or cardiac disease. We investigated whether preoperative subcutaneous liraglutide improves myocardial function after cardiac surgery. METHODS: We performed a pre-planned secondary analysis of adult patients undergoing cardiac surgery included in the GLOBE trial. Patients were randomised to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia, or matching placebo. Perioperative echocardiographic assessments, haemodynamic parameters, doses of vasoactive inotropic support and postoperative measurements of troponin, Creatine Kinase-MB , creatinine and lactate were compared between groups. RESULTS: The study population consisted of the entire intention-to-treat cohort of the GLOBE trial. In this study, 129 patients received liraglutide and 132 patients placebo. Baseline characteristics were comparable between groups. Postoperatively, 170 (65%) patients underwent echocardiography. In the liraglutide group, more patients had a normal left ventricular systolic function (68%, 59 patients) compared to placebo (53%, 44 patients), difference = 15%, 95%CI = 0-30, p = 0.049. Assessment of the right ventricle revealed no difference in function. CONCLUSIONS: Patients receiving short-term preoperative liraglutide treatment better maintained normal myocardial function after cardiac surgery. This study warrants further evaluation of the potential beneficial effects of GLP-1 receptor agonists in cardiac surgery patients.

Rapid method for intraoperative assessment of aortic coarctation using three-dimensional echocardiography.

AIMS: The availability of three-dimensional (3D) echography with its multiplanar review analysis software on board now allows detailed examination in assessing morphological details. We evaluated the feasibility of 3D echography in assessing intraoperative morphological details of aortic coarctation (CoA) and its repair. METHODS AND RESULTS: Nine consecutive children scheduled for surgery of CoA were intraoperatively evaluated. Intraoperative 3D data sets were taken and analysed online before resection of the coarctation, showing the cross-sectional area (CSA) of the proximal aorta, coarctation, and the distal descending aorta. After resection of the coarctation and extended end-to-end anastomosis, a 3D data set was recorded to analyse the CSA of the anastomosis. In nine out of nine consecutive procedures, intraoperative 3D echography permitted comprehensive viewing and measuring of CoA and its repair. In three out of nine surgical procedures, intraoperative 3D echography provided additional information to support surgical decision-making. CONCLUSION: Intraoperative 3D echography is a feasible non-invasive imaging modality for intraoperative assessment of CoA and its repair, which provides useful additional information.

Intraoperative real time three-dimensional transesophageal echocardiographic measurement of hemodynamic, anatomic and functional changes after aortic valve replacement.

The traditional intraoperative two-dimensional transesophageal echocardiography (2DTEE) has limitations in measuring left ventricular ejection fraction (LVEF) because measurements rely on geometric assumptions. The availability of online software and real time three-dimensional transesophageal echocardiography (RT3D-TEE) makes intraoperative LVEF measurements fast and easy. This is the first report of intraoperative measurement of LVEF and aortic valve area (AVA) by RT3-DTEE in a patient who received transcatheter-based transapical aortic valve implantation.

Intraoperative transesophageal echocardiography is beneficial for hemodynamic stabilization during left ventricular assist device implantation in children.

BACKGROUND: Mechanical circulatory support, with a left ventricular assist device (LVAD) is used in an increasing number of children for treatment of advanced heart failure as bridge-to-transplant. To date no data are available and no studies have defined the role of intraoperative transesophageal echocardiography (TEE) for hemodynamic stabilization during Centrimag Levitronix centrifugal pump implantation in children. METHODS: Children with therapy resistant heart failure, undergoing LVAD implantation using Berlin Heart Excor pediatric cannula connected to a Levitronix Centrifumag pump, are intraoperatively monitored using an Oldelft micromultiplane TEE. Intraoperative TEE is specially used to monitor right ventricular (RV) and left ventricular (LV) function, correct position of the cannulas and response to pharmacological treatment. RESULTS: In five consecutive patients RV function was assessed by TEE after starting LVAD Levitronix centrifugal pump. Initial RV failure presents with RV dilation and LV collapse. After titration of vasopressor and inotropic agents, RV contractility improved and thereby the filling of the LV. In one child, despite those measures the RV showed no improvement by TEE and a Levitronix right ventricular assist device to support the RV function was implanted as well. All patients could hemodynamically be stabilized before transport to the intensive care unit. CONCLUSION: The complex interaction of the RV and LV function and correct positioning of the cannula, during LVAD implantation in children with end-stage cardiac failure is improved by simultaneous visualization of cardiac performance of both ventricles and cannula positioning by means of intraoperative multiplane TEE.

Alveolar recruitment strategy and PEEP improve oxygenation, dynamic compliance of respiratory system and end-expiratory lung volume in pediatric patients undergoing cardiac surgery for congenital heart disease.

OBJECTIVE: Optimizing alveolar recruitment by alveolar recruitment strategy (ARS) and maintaining lung volume with adequate positive end-expiratory pressure (PEEP) allow preventing ventilator-induced lung injury (VILI). Knowing that PEEP has its most beneficial effects when dynamic compliance of respiratory system (Crs) is maximized, we hypothesize that the use of 8 cm H(2)O PEEP with ARS results in an increase in Crs and end-expiratory lung volume (EELV) compared to 8 cm H(2)O PEEP without ARS and to zero PEEP in pediatric patients undergoing cardiac surgery for congenital heart disease. METHODS: Twenty consecutive children were studied. Three different ventilation strategies were applied to each patient in the following order: 0 cm H(2)O PEEP, 8 cm H(2)O PEEP without an ARS, and 8 cm H(2)O PEEP with a standardized ARS. At the end of each ventilation strategy, Crs, EELV, and arterial blood gases were measured. RESULTS: EELV, Crs, and P(a)O(2)/FiO(2) ratio changed significantly (P < 0.001) with the application of 8 cm H2O + ARS. Mean P(a)CO(2)- PETCO(2) difference between 0 PEEP and 8 cm H2O PEEP + ARS was also significant (P < 0.05). CONCLUSION: An alveolar recruitment strategy with relative high PEEP significantly improves Crs, oxygenation, P(a)CO(2)- PETCO(2) difference, and EELV in pediatric patients undergoing cardiac surgery for congenital heart disease.

Three-dimensional transesophageal echocardiography: diagnosing the extent of pericarditis constrictiva and intraoperative surgical support.

The traditional two-dimensional transthoracic echocardiography (2DTTE) has limitations in demonstrating the extent of pericardial thickening in constrictive pericarditis (CP) because of poor transmission of ultrasound through the thickened anterior pericardial structures. We describe a case of CP, of unknown etiology, in which transesophageal 3DTEE equalled the accuracy of cardiac magnetic resonance in demonstrating the extent of pericardial thickening in CP.

Intraoperative cell salvage in infants undergoing elective cardiac surgery: a prospective trial.

BACKGROUND: For a long time intraoperative cell salvage was considered not to be applicable in paediatric patients due to technical limitations. Recently, new autotransfusion devices with small volume centrifugal bowls and dedicated paediatric systems allow efficient blood salvage in small children. The purpose of this prospective non-randomised study was to determine the impact of intraoperative cell salvage on postoperative allogeneic blood products transfusion in infant patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Two consecutive cohorts (122 patients) were studied. The first cohort underwent procedures between January 2004 and July 2005 with only blood salvage from the residual volume. The second cohort consisted of patients operated on from August 2005 to December 2006, with additional use of intraoperative cell salvage. The following variables were analysed: peri- and postoperative blood loss, transfusion of homologous blood products and cell salvage product, haematological and coagulation data, measured before, during and after the operation. RESULTS: Additional intraoperative cell salvage significantly enhanced the amount of cell saving product available for transfusion (183+/-56 ml vs 152+/-57 ml, p=0.003) and significantly more patients in this group received the cell saving product postoperatively. Consequently, allogeneic blood transfusion was significantly reduced in volume as well as in frequency. We did not observe any adverse effects of intraoperative cell salvage. CONCLUSION: Intraoperative cell salvage, employed as an adjuvant technique to the residual volume salvage in infants undergoing first time cardiac surgery with cardiopulmonary bypass, was a safe and effective method to reduce postoperative allogeneic blood transfusion. Considering current cell salvage related expense and the cost reduction achieved by diminished allogeneic transfusion, intraoperative cell salvage in infants demonstrated no economic benefit.

Intraoperative real time three-dimensional transesophageal echocardiographic evaluation of right atrial tumor.

Right atrial myxomas are uncommon heart tumors that can simulate nonspecific symptoms, such as fever, paroxysmal palpitations, chronic anemia, weight loss, and may escape timely diagnosis until the development of severe complications due to embolism. We present a patient with a history of palpitations. In search for the source of palpitations, a 2D transthoracic echocardiography was performed, showing a right atrial mass. Real time three-dimensional transesophageal echocardiography (RT3DTEE) was performed intraoperative and demonstrated very accurate information about the size and the morphology of the tumor. This is the first case report of a right atrial myxoma visualized intraoperatively by RT3DTEE.

Usefulness of intraoperative real-time 3D transesophageal echocardiography in cardiac surgery.

BACKGROUND: Recent advances in three-dimensional (3D) echocardiography allow to obtain real-time 3D transesophageal (RT3DTEE) images intraoperatively. METHODS: Preoperative transthoracic echocardiography (TTE) revealed: hypertrophic ventricular septum (TTE:19.3 mm), systolic anterior motion (SAM) not causing obstruction and malcoaptation of the anterior mitral valve leaflet (AMVL), and posterior mitral valve leaflet (PMVL) with severe mitral regurgitation. RESULTS: Intraoperative TEE with a x7-2t MATRIX-array transducer (Philips, Andover, MA, USA) with a transducer frequency of x7-2 t mHz, connected to a iE33 (Philips), shows us that the main mechanism and site of regurgitation was an AMVL cleft. We also measured a 24.3-mm thickness of the ventricular septum and analyzing the 3D full volume acquisition revealed that there was no SAM. CONCLUSION: Intraoperative RT3DTEE permitted comprehensive 3D viewing of the mitral valve revealing the mechanism of mitral valve regurgitation, SAM, and the exact width of the hypertrophic ventricular septum.

Minimally Invasive Mitral Valve Surgery With Endoaortic Balloon Requires Cerebral Monitoring.

After induction of anesthesia, an extra right radial artery catheter and cerebral oximetry were placed for minimally invasive mitral valve surgery. An anterolateral minithoracotomy, endoaortic balloon, and left atriotomy allowed visualization of the mitral valve. During the procedure, we observed a drop of the right cerebral oximetry saturation without a drop in right radial artery pressure. We suspected an aberrant right subclavian artery. After the endoaortic balloon was repositioned, right cerebral oximetry recovered. A postoperative computed tomography scan revealed an aberrant right subclavian artery. In this case, bilateral upper extremity arterial pressure monitoring would not have detected cerebral hypoperfusion.

Study protocol of the randomised placebo-controlled GLOBE trial: GLP-1 for bridging of hyperglycaemia during cardiac surgery.

INTRODUCTION: Perioperative hyperglycaemia is common during cardiac surgery and associated with postoperative complications. Although intensive insulin therapy for glycaemic control can reduce complications, it carries the risk of hypoglycaemia. GLP-1 therapy has the potential to lower glucose without causing hypoglycaemia. We hypothesise that preoperative liraglutide (a synthetic GLP-1 analogue) will reduce the number of patients requiring insulin to achieve glucose values<8 mmol l-1 in the intraoperative period. METHODS AND ANALYSIS: We designed a multi-centre randomised parallel placebo-controlled trial and aim to include 274 patients undergoing cardiac surgery, aged 18-80 years, with or without diabetes mellitus. Patients will receive 0.6 mg liraglutide or placebo on the evening before, and 1.2 mg liraglutide or placebo just prior to surgery. Blood glucose is measured hourly and controlled with an insulin bolus algorithm, with a glycaemic target between 4-8 mmol l-1. The primary outcome is the percentage of patients requiring insulin intraoperatively. ETHICS AND DISSEMINATION: This study protocol has been approved by the medical ethics committee of the Academic Medical Centre (AMC) in Amsterdam and by the Dutch competent authority. The study is investigator-initiated and the AMC, as sponsor, will remain owner of all data and have all publication rights. Results will be submitted for publication in a peer-reviewed international medical journal. TRIAL REGISTRATION NUMBER: NTR6323; Pre-results.

Virtual reality 3D echocardiography in the assessment of tricuspid valve function after surgical closure of ventricular septal defect.

BACKGROUND: This study was done to investigate the potential additional role of virtual reality, using three-dimensional (3D) echocardiographic holograms, in the postoperative assessment of tricuspid valve function after surgical closure of ventricular septal defect (VSD). METHODS: 12 data sets from intraoperative epicardial echocardiographic studies in 5 operations (patient age at operation 3 weeks to 4 years and bodyweight at operation 3.8 to 17.2 kg) after surgical closure of VSD were included in the study. The data sets were analysed as two-dimensional (2D) images on the screen of the ultrasound system as well as holograms in an I-space virtual reality (VR) system. The 2D images were assessed for tricuspid valve function. In the I-Space, a 6 degrees-of-freedom controller was used to create the necessary projectory positions and cutting planes in the hologram. The holograms were used for additional assessment of tricuspid valve leaflet mobility. RESULTS: All data sets could be used for 2D as well as holographic analysis. In all data sets the area of interest could be identified. The 2D analysis showed no tricuspid valve stenosis or regurgitation. Leaflet mobility was considered normal. In the virtual reality of the I-Space, all data sets allowed to assess the tricuspid leaflet level in a single holographic representation. In 3 holograms the septal leaflet showed restricted mobility that was not appreciated in the 2D echocardiogram. In 4 data sets the posterior leaflet and the tricuspid papillary apparatus were not completely included. CONCLUSION: This report shows that dynamic holographic imaging of intraoperative postoperative echocardiographic data regarding tricuspid valve function after VSD closure is feasible. Holographic analysis allows for additional tricuspid valve leaflet mobility analysis. The large size of the probe, in relation to small size of the patient, may preclude a complete data set. At the moment the requirement of an I-Space VR system limits the applicability in virtual reality 3D echocardiography in clinical practice.