Magnetic resonance imaging (MRI) is an important tool for cardiac research, and it is frequently used for resting cardiac assessments. However, research into non-pharmacological stress cardiac evaluation is limited.We aimed to design a portable and relatively inexpensive MRI cycle ergometer capable of continuously measuring pedalling workload while patients exercise to maintain target heart rates.We constructed and tested an MRI-compatible cycle ergometer for a 1.5 T MRI scanner. Resting and sub-maximal exercise images (at 110 beats per minute) were successfully obtained in 8 healthy adults.The MRI-compatible cycle ergometer constructed by our research group enabled cardiac assessments at fixed heart rates, while continuously recording power output by directly measuring pedal force and crank rotation. Magnetic Resonance Imaging (MRI) and echocardiography are the most common non-invasive methods for assessing left ventricular function and structure. Previous studies have highlighted the advantages of MRI over echocardiography ,2. MRI sMagnetic resonance imaging has become an important tool for cardiac research, and resting cardiac assessments are now routinely performed. Dobutamine stress tests during MRI scanning are commonly used to evaluate the cardiac function at a target heart rate . HoweverThus, we aimed to design a portable and affordable MRI cycle ergometer that continuously measures power, through the direct measurement of force and pedal rotation while patients exercise to maintain target heart rates. The continuously adjustable workload measurement should be capable of maintaining target heart rate, with minimum variability. For this purpose, we aimed to design an ergometer that would: a) provide variable resistance to control workload; b) allow patients to be positioned close to the MRI isocenter. We report here a custom-built MRI-compatible cycle ergometer that meets the above requirements, as well as an associated exercise protocol, both designed by our research group for left ventricular evaluation.The MRI cycle ergometer was designed to function without interfering with the scanned images. Apart from the above described requirements, it was necessary for the ergometer to: 1) accurately measure power output (up to 200 W); 2) be compact; 3) have minimal initial static and kinetic friction; 4) be easy to set up and install; 5) function over the normal range of men and women's heights; 6) have a comfortable and secure feet placements; 7) ensure minimal electronic interference on MRI image quality; 8) continuously record forces and displacements; and 9) offer resistance control.The cycle ergometer was specifically made to fit into a 1.5 T MRI scanner with a 600 mm bore , and consists of an aluminium pedal system with two force transducers, a pulley and an aluminium flywheel, a hydraulic disk brake, a rotary position encoder, and an electronic enclosure Figure  was usedc) and angular velocity (ω) of the crank. The position encoder returned a two-channel quadrature output to indicate angular motion and direction, and an additional once-per-revolution index pulse. Encoder signals interfaced with a digital position counter on a data acquisition device. The position encoder was enclosed by a customised aluminium casing to reduce electromagnetic and radio-frequency interference (EMI/RFI).A three channel optical encoder  was used to measure the angular position (Af) applied by each foot. Bridge signals were fed-through to the electronic enclosure, where an instrumentation amplifier  amplified and filtered the signals prior to digitisation. A Sallen-Key hardware filter in low pass configuration  was also implemented in the circuit. The force transducers were calibrated using a mechanical testing system (Instron 5800 series) with a 10 kN load cell. Three calibration trials were conducted on each force transducer. The force transducers exhibited a high degree of linearity (R2 = 0.999) over the specified force measurement range, with sensitivity of 14 μV/N.In order to calculate power, the force applied by the subject to each foot pedal was measured. An MRI-compatible force transducer  was integrated into each pedal to measure the extension and retraction forces  by Estimates of patient instantaneous power output were computed from the acquired force and position signals as follows. Each force transducer measures a force l Figure . The comp Ais approximately 30° throughout each rotation of the crank; we therefore assume this value for subsequent calculations. By summing the torques from each crank (yielding the net torque nτ) we compute the power (P) imparted by the patient to the ergometer as = nωt.When a patient is lying in the MRI machine with their feet attached to the footplates, we observe that A software interface Figure  for the Eight healthy sedentary volunteers  were recruited to test the MRI ergometer and exercise protocol. This protocol was approved by the Northern X Regional Ethics Committee, Auckland, New Zealand (NTX/07/12/125). All participants provided written consent and completed a health screen questionnaire prior to assessments. Body composition and fitness level were assessed one week prior to the cardiac MRI scanning. Total body scans were performed by Dual-Energy X-ray Absorptiometry . Standard manufacturers' software was used to determine fat mass, fat free mass and body fat percentage. Anthropometric data obtained from all participants included weight, height and body mass index (BMI).2max test) was measured by the patient pedalling to exhaustion on an electronically-braked cycle ergometer . The exercise protocol consisted of a 3 minute to 5 minute warm-up at a low workload (20 W to 40 W) followed by successive one-minute stages starting at 55 W, incrementing 15 W per stage. Breath-by-breath data were collected and analyzed using a ParvoMedics TrueOne 2400 Metabolic Measurement System  calibrated with room air and standardized gas. The rate of oxygen consumption (VO2) and carbon dioxide production (VCO2) were recorded every 30 s. The average of the two highest consecutive VO2 values was defined as VO2max. The test was considered a true maximum if either a plateau or an increase of less than 250 ml in VO2 occurred in spite of an increase in workload or a respiratory exchange ratio (RER) greater than 1.1 was achieved. Blood pressure was recorded both at the beginning and termination of the test.Maximal oxygen consumption  scanner using a 12 channel body matrix coil in combination with the spine matrix coil. Images were acquired with retrospective ECG-gating . The MRI-compatible cycle ergometer was positioned at the end of the scan table, and fibre optic cable fed through the waveguide to outside computer. Once a participant was positioned on the MRI table, electrodes were attached to the anterior chest wall and a blood pressure cuff was placed on the left arm . Headphones and an emergency buzzer (right hand) were also provided. The participant's feet were then strapped into pedals and their body position adjusted on table. A velcro strap was also positioned across the participant's hip to prevent upwards movement on the bed due to leg motion during cycling, In addition, a strap, attached to the left base of the ergometer, was given to each participant to hold (left hand) to ensure trunk stability during exercise. The participant then performed a short bout of unloaded exercise to gain familiarity with supine cycling and the breath hold manoeuvre. Once the ergometer initialisation was performed, the MRI table was advanced so that the subject's heart was located within 110 mm of isocenter, while ensuring that the participant's knees did not contact the bore during pedalling. The 1.5 T scanner used has a bore size of 600 mm. A bolster was then placed under the knees for comfort while resting images were obtained. If patient position was not at zero, the table position was reset before scanning.v L- 36 mm)/5 + 6 mm, where v Lis the left ventricle length. Three long-axis Trufisp images were then obtained at cine 0°, 60° and 120°. Images were acquired during breath hold manoeuvres (10 s to 15 s) with phase resolution at 100% (256 × 256). Temporal resolution was set to be 30 ms. Segments were 11 - 13 and the calculate number of phases was set to a minimum of 25. Participants performed breath-hold at end-expiration during each image acquisition, in order to eliminate respiratory motion artefacts. Blood pressure was measured after all 9 images were obtained, at the end of the resting protocol.Cardiac MRI images were obtained with iPAT . Six short-axis Trufisp cine 6 mm evenly spaced images from base to apex were obtained. The distance calculation between slices was given by: . Cycling was resumed immediately afterwards. Similarly to those obtained at rest, six short-axes and three long-axis images were acquired. It was established that phase resolution could be reduced to 50% to shorten breath hold (aimed for 128 × 256), which did not degrade the quality of the images obtained  using the six short-axis and three long-axis LV images. Cardiac parameters obtained included left ventricular mass, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, ejection fraction . Endocardial contours of each slice were manually identified at end-diastole and end-systole for each time point through the cardiac cycle. Cardiac output was determined by multiplying stroke volume by heart rate.Data obtained at rest and during exercise were compared using t-tests. The statistical package SPSS version 15.1  was used. Statistical significance was set as p < 0.05. Data are presented as mean ± standard deviation (SD).Table Cardiac results at rest and during exercise are shown on Table We have successfully designed, constructed, and tested an MRI-compatible cycle ergometer for cardiac assessments, which takes into account between-subject variations, to accurately quantify workload power. The ergometer was designed to fit into a 1.5 T MRI scanner , and is adjustable for a relatively wide range of heights.This ergometer has the potential to assist physiological studies looking at cardiac responses to dynamic exercise in a variety of populations. Moreover, the dose of exercise (workload) generated can be more precisely adjusted, which allows for the assessment of patients with varying degrees of fitness . Our ergA number of cardiac impairments are only evident when the heart is exposed to stress. Heart rate or rate pressure product (heart rate × systolic blood pressure) have the strongest association with myocardial work of all non-invasive measures . Thus, sHeart rate control is also critical in the assessment of diastolic filling properties. Peak early mitral valve inflow velocity, an indicator of diastolic function, is inversely proportional to heart rate . This isA disadvantage of the fixed resistance machine used in this study is that it is more difficult to establish a steady state workload. Indeed fixed workload machines are ideally engineered for this purpose (workload is unaffected by cadence). The fixed resistance machine used in this study is poorly suited for reproducing a relative workload  because of the dependence on pedalling cadence. However, this can be readily achieved by using a metronome to provide a pedalling cadence at which any resistance can be used to develop a desired workload with minimal difficulty.This MRI cycle ergometer demonstrated the value in obtaining MRI images during exercise at a fixed heart rate. In particular it enables identification of stroke volume which varied between 70-120 ml at rest increasing up to 200 ml during exercise, depending on ventricular morphology and fitness level -22. As eV˙O2max. The phyV˙O2max,14 (TablV˙O2max. The firV˙O2max. Even thTypically with MRI compatible cycle bikes the workload is either set at a constant level for all individuals or manually adjusted for each individual to increase and maintain heart rate at a predetermined criterion level such as 65% of maximum heart rate. According to Laperriere and colleagues 1989 a potential problem arises when manual adjustments of workload are used to produce and maintain specified heart rate. The workload value needed to maintain a predetermined heart rate percentage of maximum heart rate for a group of individuals, will be different for individuals with different pre-existing fitness levels . Also, fIn summary, the MRI-compatible cycle ergometer constructed by our research group allows for accurate and reproducible exercise cardiac assessments at tightly regulated heart rates, while continuously recording workload.2max: Maximal oxygen consumption; VO2: Rate of oxygen consumption; VCO2: Carbon dioxide production.BMI: Body mass index; ECG: Electrocardiogram; EDV: End-diastolic volume; EF: Ejection fraction; EMI/RFI: Electromagnetic interference and radio-frequency interference; ESV: End-systolic volume; LVM: Left ventricular mass; MRI: Magnetic resonance imaging; RER: Respiratory exchange ratio; SV: Stroke volume; VOThe authors declare that they have no competing interests.SG: conceived and designed the study, was involved in funding application, carried out data acquisition, analysis and interpretation, drafted and revised the manuscript. CS: was responsible for the software design. PH: participated in the coordination of the research group, involved in the acquisition of funding, participated in the writing and revision of the manuscript. WC: involved in the acquisition of funding, participated in the revision of the manuscript. JCB: involved in the acquisition of funding, participated in the revision of the manuscript. AT: participated in the design, and construction of ergometer and software interface; helped draft the manuscript. PN: participated in the design and construction of ergometer, supervised the bioengineering research group work, and helped draft the manuscript. All authors read and approved the final manuscript.


The geometry and heterogeneity of the right ventricle in hypoplastic left heart syndrome makes objective echocardiographic assessment of systolic function challenging. Consequently, subjective echocardiographic assessment of right ventricular (RV) function is still routinely undertaken. The aims of this study were to compare this with magnetic resonance imaging (MRI), investigate the impact of experience and training on the accuracy of subjective assessment, and critically analyze the role of echocardiography to detect impaired systolic function.A retrospective analysis of prospectively acquired data was performed. Children with hypoplastic left heart syndrome underwent routine preoperative cardiac MRI and echocardiography under the same general anesthetic. Echocardiograms were reviewed, and members of the congenital heart disease team with differing echocardiography experience subjectively graded RV systolic function . This was compared with MRI-derived ejection fraction.Twenty-eight patients at different palliative stages were included. Twenty-eight observers were divided into five experience categories . Median agreement was 47.6% , with the lowest agreement among junior trainees and the highest among attending cardiologists. When used as a screening test for poor RV systolic function, the median sensitivity of echocardiography was 0.89 , and median specificity was 0.45 . The highest sensitivity was observed among junior trainees but with the lowest specificity. The highest specificity was observed among attending cardiologists (0.55).Agreement between echocardiographic and MRI RV ejection fraction improves with experience but remains suboptimal. When used as a screening test for poor RV function, echocardiography is sensitive, but specificity is heavily influenced by operator experience. Hypoplastic left heart syndrome (HLHS) describes a spectrum of underdevelopment of the left heart that renders it incapable of supporting the systemic arterial circulation.The “gold standard” for the measurement of intrinsic RV contractility is by conductance catheterization, but this is not used in routine clinical practice. In the clinical care of patients with HLHS, cardiac magnetic resonance imaging (MRI)Although several echocardiographic indices have been investigated for the assessment of RV function,www.onlinejase.com]). As secondary aims, we sought to investigate the impact of observer training and experience on the correlation of echocardiographic and MRI methods, as well as the performance of echocardiography when used as a screening test to detect reduced RV EF measured on MRI.The first aim of this study was to investigate the accuracy of subjective echocardiographic assessment of systolic RV function in patients with HLHS, when compared with cardiac MRI–derived EF  undergoing cardiac MRI under general anesthesia were included in the study. At our institution, cardiac MRI is routinely used in combination with echocardiography before hemi-Fontan and total cavopulmonary connection as well as for patients after total cavopulmonary connection. Therefore, all patients with HLHS undergo MRI before hemi-Fontan and total cavopulmonary connection. Patients were excluded if parental consent was not given or if there was cardiovascular instability during the MRI scan, precluding additional time for echocardiography. Data were prospectively acquired but retrospectively analyzed for this study.MRI scans were performed on a Philips 1.5-T Achieva scanner  and were reevaluated using ViewForum EWS version 2.0 . Two-dimensional steady-state free precession cine imaging oriented to the short axis of the right ventricle was used to calculate ventricular volumes using the disk summation method. End-diastolic and end-systolic contours were manually traced (excluding major trabeculations from the volume) to determine end-diastolic volume, end-systolic volume, stroke volume, and EF.Echocardiography was undertaken immediately after the MRI scan under the same general anesthetic to avoid potential physiologic changes. Comprehensive echocardiography was performed on a Philips iE33 ultrasound system . Subcostal, apical, long-axis, and short-axis views were obtained, whenever acoustic windows permitted. Two-dimensional cine images (no color) were anonymized and reviewed by a range of observers working within the department of congenital heart disease with varying levels of experience of echocardiography in this patient group. Observers were blinded to the MRI results. Each observer was asked on the basis of the images to categorize global RV systolic function as good, moderate, or poor consistent with the normal subjective description in clinical use at our institution. This method has been used previously to compare echocardiography and MRI in both the biventricular and single-ventricle setting.n = 5), junior fellows with <3 years of training (n = 6), senior fellows with >3 years of training (n = 5), cardiac physiologists (n = 5), and attending cardiologists (n = 7). Further delineation of the experience of each group is given in the Observers were grouped by experience level: residents with <6 months' exposure to echocardiography . For example, if an MRI EF was good (>50%) and the observer rated it as poor echocardiographically, this was considered two grades different. Each observer was given a total score ; this was then averaged for each observer experience group. Thus, a low score means that there was a high level of agreement between the echocardiographic assessment and MRI, and a high score indicates worse agreement between the echocardiographic and MRI methods. To evaluate variability in assessment in each observer group, intraclass correlation coefficients were calculated within in each observer group .An important clinical consideration is the ability of echocardiography to accurately detect reduced RV systolic function. If an RV EF of <50% assessed by MRI is regarded as “reduced function,” sensitivity, specificity, positive predictive value, and negative predictive value of subjective echocardiographic function were calculated for each observer group. Echocardiographically assessed moderate or poor function was taken to indicate reduced function.All MRI scans were analyzed by two observers (H.R.B.-R. and A.J.B.). All echocardiograms were graded for quality by the same two observers. Scans were graded from 1  to 4 . Intraclass correlation coefficients were calculated to assess interobserver variation for MRI analysis .Twenty-eight patients with HLHS underwent echocardiography under the same general anesthetic as MRI between July 2007 and January 2009. All patients had magnetic resonance and echocardiographic images available for analysis. The demographics and MRI results are shown in Interobserver variability for MRI analysis showed good concordance. Intraclass correlation coefficients were 0.945 , 0.952 , 0.926 , and 0.885  for end-diastolic volume, end-systolic volume, stroke volume, and EF, respectively.When evaluating the echocardiograms, there was a trend toward improved concordance with increasing experience . AttendiFor the analysis of the performance of subjective echocardiographic assessment to detect reduced RV EF (<50%) by MRI, the sensitivity, specificity, positive predictive value, and negative predictive value (on the basis of group averages) are shown in In routine clinical practice in the outpatient clinic, inpatient ward, or perioperative setting, echocardiography is the mainstay of assessment of RV systolic function in patients with HLHS. Although many qualitative techniques to determine systolic and diastolic function have been described,In this retrospective study, we sought to evaluate the accuracy of subjective assessment of RV systolic function in patients with HLHS, as well as investigating whether this was determined by operator experience. We have shown that visual assessment of RV systolic function has only a limited correlation with MRI EF but that this appears to improve with increasing levels of experience . Even inAn important role of echocardiography in the sequential assessment of patients with HLHS is to detect RV dysfunction. Our analysis of echocardiography to detect reduced RV EF (<50%) on the basis of MRI was undertaken to address this question. The observer group with the highest sensitivity to identify reduced RV EF was the residents, who have the least echocardiographic experience. This finding was matched, however, by the lowest specificity for residents, in contrast to the highest specificity observed among attending cardiologists, the most experienced group. We speculate that because of the important clinical implications of RV dysfunction in this patient group, that less experienced observers will “overcall” echocardiographically reduced RV systolic function to avoid missing patients with clinically significant ventricular impairment. More experienced observers may be more likely to trust their assessments of echocardiograms and be more confident that ventricular impairment is absent. If echocardiographic judgment of impaired ventricular function leads to further corroborative imaging such as MRI, then fewer patients would be referred for such imaging in the hands of more experienced observers.The improvement seen with increasing experience is likely to be due to increased exposure to both echocardiography and MRI, often in the context of cardiac surgical conferences, where decisions are made with respect to patient management. Our results emphasize the need for more robust and objective echocardiographic tools for the sequential assessment of patients with HLHS. This is particularly important because of the noninvasive nature and ready repeatability of echocardiographic techniques for sequential assessment. Methods using Doppler tissue imaging and speckle tracking are currently being investigatedThe majority of patients had MRI EF in the normal range. This is likely to represent a degree of selection bias, as those with very poor function are at greater risk for mortality.This study has shown that subjective assessment of RV function in patients with HLHS is limited but improves with increasing experience. This has important clinical implications, as junior staff members perform the majority of assessments, particularly in the immediate postoperative period, and emphasizes the importance of ongoing training and supervision. Objective echocardiographic measures to reliably measure RV function in these patients are required. Ideally, these would be simple, reproducible, and not altered by the patient's operative stage, loading conditions, or morphologic subtype.


In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT). HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI) are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock. After 7 decades of clinical use, heparin still remains the most commonly used anticoagulant in clinical practice. Heparin use in medical practice is increasing due to the increase in the number of vascular interventions and aging population. It is estimated that up to 30% of in-hospital patients need some form of heparin during their hospital stay and 600,000 new cases of heparin-induced thrombocytopenia (HIT) are reported every year.Thrombocytopenia is one of the common abnormalities in critically ill patients. It is caused by different conditions from sepsis to intravascular devices and it is closely related to the outcome of these intensive therapy unit patients.3 /L, from 5 to 14 days of therapy.[HIT is a clinicopathologic, procoagulant condition with thrombocytopenia in patients on heparin therapy, decrease in platelet count by 50% or to less than 100 × 10The incidence of HIT varies with type and duration of heparin used. Incidence is significantly lower, when low–molecular weight heparin (LMWH) is used. When com4HIT is divided into 2 types, depending on whether immunologically mediated or not.Type 1 HIT or nonimmunologically mediated thrombocytopenia or heparin-associated thrombocytopenia, is associated with a larger dose of heparin and occurs earlier, caused by direct nonimmune platelet activation by heparin; it is self-limiting, asymptomatic, and without any complications.Type 2 HIT or immunologically mediated thrombocytopenia is caused by heparin-dependent antibodies. It is subdivided into (a) heparin antibodies without any thrombocytopenia; (b) isolated HIT, thrombocytopenia with antibodies; and (c) HITT or HIT thrombotic syndrome or white clot is HIT with thrombosis.When due to any etiologic reason, Virchow’s triad/vascular injury occurs, the tissue factor is activated from the damaged endothelium, which combines with factor vii, and activates coagulation cascade, leading to thrombin generation. Thrombin is the chief factor in the coagulation process; it converts fibrinogen to fibrin, and also activates coagulation factors V, VIII, and XI, which in turn produce more thrombin. In combination with factor xiii, thrombin favors the formation of cross-linked hard clot Hypercoagulable state in HIT patients is multifactorial. In these patients, there is platelet activation with the formation of procoagulant PF4/heparin/immunoglobulin complex, increase in thrombin generation, activation of intrinsic tissue factor, and neutralization of anticoagulant effect of heparin.Heparin is a negatively charged polysaccharide, and it forms an immunologic complex by combining with the positively charged platelet factor 4 (PF4). PF4 is released from platelet storage granules during the activation of platelets. LMWH wraps around PF4 to a much lesser extent as compared with the unfractional heparin (UFH), hence the incidence of HIT is lower in patients on LMWH. This binFew of the main risk factors for the development of HIT are high dose of intravenous UFH, UFH, bovine heparin, and patients undergoing surgery.HIT is manifested by thrombocytopenia between 5 and 15 days of heparin treatment. Clinical scoring to diagnSimple platelet monitoring is important for early diagnosis and prompt recognition of HIT. If a patient is on full dose of UFH, daily platelet count monitoring is a must, or receiving intermediate dose of UFH or platelets should be monitored every other day, but when the patient is receiving LMWH or low dose UFH, twice a week monitoring of platelet count is enough. There arHIT has to be differentiated from disseminated intravascular coagulation (DIC), heparin toxicity, and hyperresponsive thrombocytopenia. It is critical to differentiate these conditions from HIT as their management is totally different from that of HIT.DIC is a pathologic activation of intravascular coagulation leading to thrombocytopenia and bleeding due to various diseases ranging from sepsis to trauma and obstetrical causes. In DIC the endovascular injury leads to small vascular thrombosis with consumption of coagulation factors and platelets. Thrombocytopenia of DIC can be differentiated from HIT by bleeding tendency, prolonged coagulation parameters, and elevated fibrinogen degradation products.Acute heparin toxicity is the heparin overdose, which can be life threatening and fatal. Common manifestations are bleeding from wound, mucosal membrane, and more critical intraventricular hemorrhage. It can be differentiated from HIT by bleeding, abnormally prolonged activated prothrombin time with thrombocytopenia.Hyperresponsive thrombocytopenia occurs in various inflammatory diseases, such as eczema, allergic rhinitis, and bronchial asthma. Particularly, the platelets are actively involved and consumed in acute bronchial asthma leading to bronchial hyperresponsiveness, bronchoconstriction with airway inflammation, and thrombocytopenia. It can be differentiated from HIT by the signs and symptoms of primary etiology leading to hyperactive response.Mainly the following complications are seen in HIT patients: venous/arterial thrombosis, skin lesions, and acute platelet activation syndrome.Venous thromboembolic complications are 4 times more common than arterial thrombosis. Mainly tSkin necrosis or erythematous plaques can occur at the site of heparin injections. Acute platelet activation syndrome will manifest as acute inflammatory response with fever and chills. Despite severe thrombocytopenia, hemorrhage is not a characteristic complication of HIT.Alterative anticoagulants are required in HIT patients with thromboembolic phenomenon or routine essential procedures  or emergencies, such as acute coronary syndrome.The alternative anticoagulant should not generate HIT antibodies or cross-react with antiheparin–platelet factor 4 antibodies. The important aspects of selection of these agents are familiarity with the agent, its dosage, safety and efficacy, patient’s condition and hepatic and renal functions, clearance of agents, and availability of the monitoring techniques.The alternative anticoagulant agents to heparin are direct thrombin inhibitors (which directly inhibit thrombin generation) danaparoid, Fondaparinux (selective factor X inhibitors), and warfarin (vitamin K antagonist). Details of the pharmacodynamics and pharmacokinetics of these agents are discussed in the Treatment section.As the highest risk for development of thrombosis is from the time of diagnosis of HIT to the starting of antithrombin agents, the management of HIT patient should be started without delay and waiting for the results of confirmatory laboratory tests. The treaVarious anticoagulant therapies are investigated over the last decade for the treatment and prevention of new thrombosis in HIT patients. LMWH are contraindicated in patients with HIT due to its cross-reaction with heparin antibodies, and in acute HIT phase warfarin is contraindicated as it paradoxically worsens the thrombosis due to a drastic decrease in protein C levels.The Direct Thrombin Inhibitors (DTI) are the medication of choice in patients with HIT or interventions where heparin is indicated but cannot be used, as these agents neither interact with heparin-dependent antibodies nor do they need an antithrombin as a cofactor . DTI havLepirudin should be monitored 4 h after the initiation of therapy; and the target activated partial thromboplastin time (aPTT) is 1.5–2.5 times of mean reference value. Desirudin does not need monitoring except in patients with renal impairment. Bivalirudin should be monitored by activated clotting time (ACT), in patients with renal insufficiency or increased risk of bleeding. Group 2 DTI or monovalent DTI, argatroban is l-arginine-based molecule. It is shBleeding is the major concern for all DTI, risk of bleeding is higher with lepirudin and desirudin when compared with argatroban and no specific antidote is available for DTI. In a proet al demonstrated that there was a significant reduction in death, amputations, new thromboembolic events, and quick rise in platelet levels in the argatroban group compared with the control group.[In another study, Lewis ol group.The warfarin therapy needed in HIT patients should be delayed till the platelet count reaches >100,000. DTI should be continued at least for 5 days with warfarin therapy and international normalizing ratio in therapeutic range for 2 days.28A few more medications, such as danaparoid sodium and Fondaparinux, are also used in HIT patients for the treatment and prevention of thrombosis.Danaparoid is a heparinoid compound, it interacts with antithrombin III to inhibit factor Xa. It is widely used in the treatment of HIT patients, in spite of cross-reactivity with antibodies in about 15% of the patients.Fondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa. It is FDA approved for anticoagulation and deep venous thromboprophylaxis. A small study showed no cross-reactivity of Fondaparinux with HIT antibodies.A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention (PCI), and Cardiopulmonary Bypass (CPB); but cannot be used if the patient develops HIT. HIT patients with unstable angina, thromboembolism, indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy.HIT antibodies are positive in up to 17% of the patients on hemodialysis and mortality in these patients is significantly high. The manifestation of HIT in these patients varies from acute systemic reaction to frequent clotting in the extracorporeal circuit or increase in the number of failed arteriovenous fistula.As soon as HIT is suspected in these patients, all forms of heparin should be stopped and start DTI or danaparoid or regional citrate anticoagulation. Argatroban has advantage in these patients as no dose adjustment is required; the recommended dose is an initial bolus of 250 mcg/kg at the start of dialysis then continuous infusion of 2 mcg/kg/min until 1 h before the end of dialysis session. Only bolus dose of lepirudin recommended at the beginning of dialysis session. This DTI therapy should be monitored with aPTT and dose can be adjusted accordingly. For initial 2 dialysis sessions, the dose of danaparoid is 2500 units, then in the subsequent dialysis sessions the dose should be decreased to 2000 units and anti-Xa has to be monitored and maintained in the range of 0.5–0.8 units/mL.Hypercoagulability in HIT patients in combination with endovascular disruptions PCI and CPB will particularly increase the risk of thrombosis. Argatroban, bivalirudin, and danaparoid are commonly used in PCI and the dosages are as follows: an initial bolus dose of bivalirudin should be 0.75 mg/kg, followed by 1.75 mg/kg/min; argatroban bolus of 350 mcg/kg followed by 25 mcg/kg/min infusion with ACT monitoring; and danaparoid 2200 unit bolus followed by 150–200 units/h with anti-Xa levels monitoring.If possible CPB surgeries should be postponed till PF4-heparin antibodies negative. If surgery has to be done, bivalirudin, lepirudin, argatroban, or danaparoid can be used.These patients may need full anticoagulation for days; intravenous argatroban is used successfully in HIT patients with unstable coronary syndrome.In patients with multiple organ dysfunction/failure who are critically ill and may have hepatic/renal impairment or failures, the dose of DTI should be adjusted with meticulous monitoring of the coagulation parameters, but drug accumulation and lack of antidote will put these critical patients at the risk of potential side effects. Bivalirudin demonstrated better safety as it is cleared predominantly by the enzymatic cleavage.When a HIT patient becomes pregnant may require thromboprophylaxis and/or treatment for thrombosis; danaparoid, subcutaneous lepirudin, and Fondaparinux are used successfully, but limited literature is available about their effects on fetus and newborn.Early diagnosis and management of HIT can limit the morbidity and mortality of suffering patients. Reported mortality is up to 30%, and as high as 20% of HIT patients with thrombosis need amputation. In HIT pMany other therapies and medications, such as antiplatelet agent and ancrod defibrogenating snake venom, are tried but showed poor efficacy and increase in thrombin generation.Small doses of thrombolytic agents were used locally in HIT patients with good results in massive pulmonary embolism or arterial thrombosis.Ralph–Edward successfully managed a case of massive pulmonary embolism in a patient with HIT by embolectomy.The following measures will decrease the incidence of HIT as well as coagulation disorders.Keeping heparin therapy for shorter duration and starting warfarin early if expecting prolonged anticoagulation.Avoiding bovine and fractional heparin and using LMWH.40Stopping the use of heparin flush for central and arterial catheters.Heparin-free dialysis and not using heparin lock.Heparin is the commonly used anticoagulant; about 30% of hospitalized patients are exposed to some form of heparin. Most feared complication of heparin use is HIT. HIT is a clinicopathologic, procoagulant condition with thrombocytopenia in patients on heparin therapy, with decrease in platelet count by 50% or to less than 100 × 103/L, from 5 to 14 days of the therapy. It is diagnosed by 4 “T”s thrombocytopenia, timing, thrombosis absence of other causes for thrombocytopenia, and the diagnosis is confirmed by immunoassay. HIT is common in surgical and orthopedic patients. The risk of HIT is more with high dose of intravenous heparin and bovine heparin. Deep venous thrombosis and pulmonary artery embolism are common in HIT patients. Management of HIT is to stop heparin, and DTI are backbone of HIT therapy. Few cases of successful pulmonary embolectomy and arterial thrombolysis in HIT patients with massive pulmonary and arterial thrombosis are reported. Mortality in HIT patients can be as high as 30%, but it can be significantly reduced with the use of DTI to 16%. A few routine but essential procedures performed by using heparin are hemodialysis, PCI, and CPB; but cannot be used if the patient develops HIT. HIT patients with unstable angina, thromboembolism, indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using LMWH, and by stopping the use of heparin flush and heparin lock.


Patients with ischemic cardiomyopathy (CMP) often develop regional wall motion abnormalities (WMA) due to myocardial scarring, stunning or hibernation. Abnormal functioning myocardial segments without evidence of fibrosis on late gadolinium-enhancement cardiac magnetic resonance (LGE-CMR) are felt to represent stunned or hibernating myocardium, presumably with significant coronary artery disease (CAD) in the vessel supplying the region. We analyzed the association between segmental wall motion abnormalities (WMA) and underlying CAD in ischemic CMP.53 consecutive patients referred for LGE-CMR with recent coronary angiography (< 2 weeks from index CMR) and evidence of ischemic CMP on LGE-CMR  were included. CMR was analyzed using AHA 17-segment model for regional function and late gadolinium enhancement (LGE) as well as global left ventricular (LV) size and function. Myocardial segments were assigned to angiographic coronary artery territories based on AHA standardized segmentation for correlation of CMR and angiographic data.Of 901 segments, 638 (71%) had WMA, with severe WMA in 378 (42%). In contrast, only 340 (38%) had LGE, including 233 (24%) with >50% transmural LGE, consistent with larger extent of WMA compared to LGE. No significant correlations were found between segments with any WMA and >50% transmural LGE . Of the 53 patients with ischemic CMP by LGE-CMR, 47 patients (89%) had documented coronary artery disease by angiography. There was no significant correlation between number of vessels with severe stenoses (>70%) and any WMA . Additionally, the number of segments with evidence of any WMA was more extensive than number of segments supplied by severe stenoses.Patients with ischemic CMP demonstrate extensive LV WMA out of proportion to the extent of myocardial scarring and epicardial CAD. These findings suggest that additional mechanisms such as microvascular disease, LV remodeling, inflammation or hibernation extending into other myocardial segments not supplied by a critical stenosis may contribute to the degree of WMA in patients with ischemic CMP.


T1 mapping is a newer technique for characterizing the myocardium, however regional variations in the healthy left ventricle are not yet fully explored, complicating interpretation of observed pathologic differences.4 in H2O, NaCl) phantom were obtained at several simulated heart rates.We assessed regional variation in T1 in the septum of patients with no left ventricular pathology. An adjunct phantom study was performed to assess whether location closer to a surface coil affected T1. Main study: Retrospective. 40 patients whose cardiac MRI showed no left ventricular disease were identified. Patients were imaged on a Siemens Avanto 1.5T scanner with a 32-channel cardiac coil. All patients had a 4-chamber TI scout approximately 12 minutes post injection of 0.14 mmol/kg gad-BOPTA. QMASS  was used to generate T1 maps and measurements obtained in small regions of interest throughout the septum. Basal, middle third, and apical regions were evaluated in all 40; a subset of 15 patients had an additional roi placed halfway between the middle and apical ROIs. Adjunct study: TI scout and MOLLI images of a liquid phantom . Midventricular septum 388 ±44 ms (271-477). ¾ distance base to apex along the septum, 356 ±56 ms (233-456). Apical septum 346 ±52 ms (197-459).By 2-tailed paired t-test, T1 of the basal vs. mid-ventricular septum was not significantly different (p=0.33). However, mid-ventricle was different from ¾ (p=0.008) and apical septum (p<0.0001) with paired t-tests. Unpaired t-test comparison of midventricular to apical septum showed p=0.0002 likelihood that the difference was due to chance.In the homogeneous T1 liquid phantom, the intra-study T1 difference  derived from TI scout imaging was 7-15 ms, from MOLLI 10-35 ms. There was thus less intra-study regional variation using the TI scout. However, whole-phantom T1 measured by TI scout was more affected by heart rate (288-314 ms) than MOLLI (314-316 ms).1) We found a gradient of T1 over the distal half of the septum. The findings may reflect a systematic artifact, or a true regional difference in septal myocardial T1. In either case, the implication is that exact slice location may be important when performing T1 mapping.Work is currently underway to explore whether this finding reflects a true difference in regional myocardium, or an artifact. Possible explanations include: regional differences in extracellular volume, collagen, or fat content of the normal septum, effects of fiber orientation, regional perfusion / gadolinium kinetics, volume averaging of blood pool related to curvature of the distal septum, motion effects, and susceptibility artifacts related to proximity to lung vs mediastinal tissues.2) Phantom studies excluded the possibility that this variation is due simply to the fact that the apex is closer to the receiver coil.none


Patients with acute myocarditis and healthy volunteers were studied to assess the ability of T2 mapping to detect myocardial edema. The T2 maps detected global and regional edema in patients. T2 mapping may be an alternative to STIR images for detecting myocardial edema in patients with acute myocarditis.In patients with acute myocarditis, T2-weighted cardiovascular magnetic resonance (CMR) can visualize myocardial edema and is used for one of the three recommended diagnostic CMR criteria. There are, however, significant technical problems associated with the short-tau-inversion-recovery (STIR) sequence, limiting its clinical utility. Quantitative T2 mapping technique may overcome such technical limitations and thus improve the diagnostic yield of CMR. Its clinical utility, however, has not been assessed. The purpose of this study is to assess the ability of T2 mapping to detect myocardial edema in patients with acute myocarditis.Ten healthy volunteers and 17 patients with acute myocarditis as diagnosed using clinical and CMR criteria (Lake Louise criteria) and evidence for myocardial edema were studied. CMR studies included STIR images, early and late gadolinium enhanced images and T2-mapping images using a T2-prepared single-shot SSFP acquisition with three T2-prep echo times: 0, 24, and 55 msec. Three short axis T2 mapping images were obtained. Global myocardial T2 values were evaluated on each slice and the mean value of 3 slices were calculated for each subject. Images were also analyzed based on a 16-segment model. T2 values were evaluated in regions of interest in each segment. T2 maps were also visually assessed to determine the location of visually abnormal and remote segments. On the slices where no visually abnormal segments were found, all segments were considered remote.The global T2 value in myocarditis patients were significantly higher than those in volunteers . Of 402 available segments, 7 segments had to be excluded due to poor image quality. A total of 129 segments in volunteers and 266 in patients were analyzed. Ninety-three segments in patients were visually identified as abnormal on T2 maps. T2 values of visually abnormal segments were significantly higher than segments in volunteers  and remote segments . In patients, T2 values of remote segments were also significantly higher than those in volunteers .For detecting myocardial edema in patients with acute myocarditis, T2 mapping may be an alternative to T2-weighted STIR imaging.N/A


Myotonic dystrophy type 1 (MD1) is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1.Eighty MD1 patients underwent physical examination, electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR). Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length.Functional and structural abnormalities were detected in 35 patients (44%). Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%). In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04), male gender (p < 0.001) and abnormal ECG (p < 0.001). Disease duration, CTG repeat length, severity of neuromuscular symptoms and NT-proBNP level did not predict the presence of myocardial abnormalities.CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration. Myotonic dystrophy type 1 (MD1), or Steinert’s disease, is an autosomal dominant inherited disorder caused by an unstable expansion of a repetitive trinucleotide sequence (CTG) on chromosome 19. The prevalence varies from 2.1-14.3 per 100 000 [Patients with MD1 usually die from respiratory or cardiac complications ,4. SuddeConsidering the importance of cardiomyopathy as a predictor of prognosis, we aimed to measure cardiac function and detect structural abnormalities in patients with MD1. We used cardiovascular magnetic resonance (CMR) in the current study since it is an accurate and highly reproducible technique for the assessment of cardiac volumes, function, mass and focal fibrosis and the interstudy reproducibility in normal, dilated, and hypertrophic hearts was superior to 2-dimensional echocardiography .The protocol was approved by the local Medical Ethics Committee and each participant gave written informed consent. Patients older than 18 years of age were invited for a prospective, on-going study on cardiac involvement and early stratification of arrhythmogenic risk. Participants were recruited from the genetic register of the Maastricht University Medical Centre and through the Dutch neuromuscular patients’ association . Subjects with previously implanted pacemakers or implantable cardioverter-defibrillators or with severe comorbidity leading to reduced life expectancy such as malignant disease or respiratory failure, were excluded. During a 2 year period, 80 consecutive patients underwent CMR imaging and were enrolled in this study.A standardized interview was conducted in all participants to evaluate their clinical history and current symptoms. A neurological and cardiac evaluation was conducted by the same examiner (MH) in a predefined standardized fashion. The MD1 phenotype was established according to the commonly accepted classification based on the age at onset of symptoms: mild (late onset), classical (adult onset) and childhood/congenital type . SkeletaAnalysis of the MD1 CTG repeat length was performed on peripheral blood lymphocytes. Polymerase chain reaction followed by fragment length analysis was used to determine small allele lengths of 5 to 100 repeats, and Southern blotting was used to estimate repeat lengths >100. For purposes of statistical analysis, the CTG expansions were divided in 4 categories .ECG was considered abnormal if signs of conduction disease , hypertrophy (Sokolow-Lyon index ≥35 mm), myocardial infarction or rhythm other than sinus, were present.Echocardiography was used to exclude significant valvular disease, elevated right ventricular systolic pressure. Transthoracic echocardiograms were performed using a SONOS 5500 system with S3 transducer . Echocardiographic investigations were performed according to the recommendations of the American Society of Echocardiography.°, FOV 350 mm, matrix 256 x 256, 22–25 phases per cardiac cycle) in two-chamber, three-chamber and four-chamber view and a short-axis stacks covering the entire LV. For the detection of myocardial edema multislice short axis images were acquired using a dual-inversion black-blood T2-weighted sequence with fat suppression . After intravenous contrast administration (Gd-DTPA 0.2 mmol/kg) a Look-Locker sequence  was applied to determine the inversion time (TI) to optimally “null” LV myocardium  for the subsequent scan. To evaluate the presence of myocardial late gadolinium enhancement (LGE) a breath-hold 3D inversion recovery gradient echo sequence covering the entire LV  segmented partial echo readout every heartbeat, flip angle 15, field of view 400 mm, matrix 256 x 256, acquired and reconstructed pixel size 1.56 x 1.56 mm, typically 16–18 slices) was used with images in short-axis, two-chamber and four-chamber view, acquired 10 minutes after the administration of intravenous contrast.Patients were examined in supine position with a clinical 1.5 T Gyroscan Intera MR scanner  equipped with a 5 channel cardiac surface coil. ECG-gated cine images were acquired for functional analysis during multiple breath holds (10–13 seconds) using a steady-state free precession sequence . Endocardial and epicardial contours were manually traced in end-diastolic and end-systolic phases on short axis cine images to determine end-diastolic and end-systolic volume, ejection fraction and LV end-diastolic mass. Systolic LV dysfunction was defined as an ejection fraction <55% or regional wall motion abnormalities. LV and right ventricular (RV) dilatation were defined as enddiastolic volumes >2SD and RV systolic dysfunction as ejection fraction <2SD of mean reference values normalized for gender, body surface area and age . We consU test. Multiple group comparisons were made with Kruskal-Wallis test. All analyses were performed using SPSS software version 15.0. A probability (p) value of <0.05 at a two-sided level was considered statistically significant.Descriptive statistics of clinical characteristics, electrocardiographic findings and cardiac magnetic resonance results are presented. Categorical variables were summarized by frequency counts (percentage) and differences between groups were evaluated using chi-square test. For continuous variables, results are presented as median (range) and comparison between categories was made with Mann–Whitney Characteristics of 80 MD1 patients  are shown in Table t-test, p < 0.001) [Functional or structural abnormalities were detected with CMR in 35 patients (44%). The results of CMR analysis are summarized in Table < 0.001) . Right vFocal myocardial fibrosis was detected on LGE images in 10 patients, most often as midmyocardial enhancement of the septal segments and basal (inferio) lateral segments of the LV wall (n = 8). Subendocardial and partly transmural enhancement of the basal lateral wall was also found n = 2). Examples of selected CMR images are shown in Figure . ExampleElectrocardiographic findings are summarized in Table Echocardiography ruled out hemodynamically significant valvular disease or elevated right ventricular pressures in all patients.A graphic reproduction of the cardiac evaluation is shown in Figure The principal finding of this study is that structural and functional myocardial abnormalities are frequent in MD1 patients. The presence of mild to moderate left ventricular systolic dysfunction, ventricular dilatation, myocardial hypertrophy or fibrosis was strongly associated with electrocardiographic conduction abnormalities. However, 16% of patients with a normal ECG still had myocardial alterations. These findings lend support to the concept that the myocardium is generally involved in the pathogenic process of MD1.Myocardial involvement may be prognostic in predicting death in MD1 . CMR is Fibrosis is a frequent histopathological finding in individual MD1 cases -23. FocaThe low prevalence of symptomatic heart failure in MD1 is usually partly attributed to the reduced cardiac demand due to diminished skeletal muscle activity . This loIncreasing age, male sex and ECG conduction abnormalities are all significantly associated with myocardial disease, whereas CTG repeat length and severity of muscular impairment are not. Male gender and age have been positively associated with arrhythmia and conduction abnormalities . There iStructural and functional cardiac changes were found in patients with mild as well as severe neurological phenotypes. Duration of neuromuscular disease was not significantly related to cardiac disease, indicating that cardiac manifestations can precede, coincide with or succeed skeletal myopathy. It should however be stressed that recall of age at onset is sometimes poor and unreliable, as the diagnosis is often considerably delayed. Furthermore, duration of symptoms do not necessarily relate to the severity of neuromuscular symptoms as disease progression is highly variable. Symptoms of dyspnoea or fatigue were not associated with LV dysfunction and may therefore largely be ascribed to the progressive physical disability of the muscular disease.The current study is a descriptive study of a large cohort of patients with MD1 using state of the art diagnostic technology. A limitation of the descriptive survey is the absence of a comparison group or prognostic data allowing no inferences to be drawn about cause of disease and the predictive value of myocardial fibrosis or other CMR findings for identifying patients with MD1 who are at risk for cardiac death.Subclinical cardiomyopathy in patients with MD1 is frequently observed with CMR. Screening for functional and structural cardiac disease should be considered in all patients since myocardial involvement can be overlooked by ECG alone. Whether the identification of structural or functional cardiac changes has prognostic implications for the prediction of disease progression or sudden death remains to be investigated in a long-term prospective study.CI, Confidence interval; CMR, Cardiovascular magnetic resonance; CTG, Cytosine-thymine-guanine; MD1, Myotonic dystrophy type 1; ECG, Electrocardiogram; LGE, Late gadolinium enhancement; MRC, Medical research council; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; LV, Left ventricle; OR, Odds ratio; RV, Right ventricle; SD, Standard deviation.The authors declare that they have no competing interests.All authors have contributed significantly to the work and have read and approved the manuscript. CF, CD-S and YP designed the study. Cardiac magnetic resonance imaging studies were analyzed by SS, SB and GS. MG did the analysis of the DMPK gene CTG repeat. Collection and interpretation of other data was done by IM and MH. Eventually, MH drafted the manuscript and all authors made critical revisions.


LL) acquired by free breathing single heart-beat fast strain encoded imaging (fast-SENC) in relation to global ventricular dysfunction markers and pulmonary hemodynamics in PH patients.Right ventricular (RV) function is the most important determinant of survival in patients with pulmonary hypertension (PH), thus monitoring of RV function is critical. However, RV regional function assessment is challenging using current MR tagging techniques. Thus, the purpose was to evaluate regional longitudinal ventricular deformation .48 subjects [35 PH patients  and 13 age and gender matched controls] were examined using short axis fast-SENC MRI and cine imaging. All patients underwent right heart catheterization (RHC). Segmental (15 RV and 16 LV segments), slice , as well as mean (average of segments) peak systolic ELL at all RV levels compared to controls  except the inferior and inferior septal insertion at all levels , pulmonary vascular resistance index  as well as reduced RV systolic function parameters   and antero-septal regions . Reduced LV antero-septal ELL correlated with increased mPAP , increased septal eccentricity index  and reduced RV systolic function . On multiple linear regression including mPAP, RV end-diastolic volume index and RV mass index as covariates, mPAP was an independent predictor of reduced mean RV ELL . In turn, reduced mean RV ELL was the main predictor of reduced RVEF in PH patients  in a model including mPAP, mean RV ELL and RV mass index. In PH patients with maintained global RV function, regional ELL was reduced at the basal and mid anterior septal insertions as well as mid anterior RV segments .PH patients demonstrated reduced Es Figure . On regils Table . Reduced) Figure . In the LL measured by fast-SENC is associated with increased afterload and correlates with biventricular global dysfunction. RV strain analysis using fast-SENC can detect subclinical regional dysfunction in absence of global RV functional compromise.In PH patients, reduced RV E


Quantification of cardiovascular magnetic resonance (CMR) myocardial perfusion reserve (MPR) at 1.5 Tesla has been shown to correlate to invasive evaluation of coronary artery disease (CAD) and to yield good inter-observer agreement. However, little is known about quantitative adenosine-perfusion CMR at 3 Tesla and no data about inter-observer agreement is available. Aim of our study was to evaluate inter-observer agreement and to assess the diagnostic accuracy in comparison to quantitative coronary angiography (QCA).Fifty-three patients referred for coronary x-ray angiography were previously examined in a 3 Tesla whole-body scanner. Adenosine and rest perfusion CMR were acquired for the quantification of MPR in all segments. Two blinded and independent readers analyzed all images. QCA was performed in case of coronary stenosis. QCA data was used to assess diagnostic accuracy of the MPR measurements.Inter-observer agreement was high for all myocardial perfusion territories . Compared to QCA receiver-operating characteristics yielded an area under the curve of 0.78 and 0.73 for RCA, 0.66 and 0.69 for LAD, and 0.52 and 0.53 for LCX perfused territories.Inter-observer agreement of MPR quantification at 3 Tesla CMR is very high for all myocardial segments. Diagnostic accuracy in comparison to QCA yields good values for the RCA and LAD perfused territories, but moderate values for the posterior LCX perfused myocardial segments. Visual assessment of perfusion cardiovascular magnetic resonance (CMR) at 1.5 Tesla has been shown to yield high diagnostic accuracy in comparison to coronary x-ray angiography for the detection of coronary artery disease (CAD) .Perfusion CMR at 3 Tesla has increased signal-to-noise and contrast-to-noise ratios in comparison to 1.5 Tesla . MoreoveIntra- and interobserver agreement for the visual assessment of adenosine-perfusion CMR as well as interstudy reproducibility of quantitative assessment at 1.5 Tesla have been proven to be very high ,10. MoreThe aim of our study was to evaluate the inter-observer agreement of quantitative myocardial perfusion analysis at 3 Tesla and to assess its diagnostic accuracy in comparison to quantitative coronary angiography (QCA).Sixty-three consecutive patients suspected for CAD or progression of known CAD, who were referred for diagnostic coronary angiography, were prospectively recruited. Patients were excluded, if they had a recent history of myocardial infarction (within 30 days), had previously undergone coronary artery bypass or prosthetic valve surgery, were medically unstable, and had contraindications for gadolinium-based contrast agents, adenosine infusion, or CMR. Study patients were asked to avoid caffeine or other methylxanthines for at least 24 hours before CMR. All patients underwent CMR within 72 hours before of coronary catheterization. The study was approved by the ethics committee of the institution. All participants gave written informed consent.All patients underwent CMR in a 3 Tesla whole-body system  using a 32-channel phased-array cardiac surface coil . Heart rate and blood pressure were monitored non-invasively during adenosine infusion. The CMR protocol used has been previously described in detail .For functional analysis of the left and right ventricle a balanced steady-state free precession sequence was acquired in contiguous short-axis views covering the entire left and right ventricle from apex to basis .For perfusion imaging a spoiled gradient-echo sequence  was acquired in three short axis . After three minutes of adenosine infusion at a constant rate of 140 μg/kg/min, or earlier if angina pectoris was provoked, a bolus of 0.075 mmol/kg contrast agent  followed by 20 ml saline flush was administered with an injection rate of 5 ml/s. The sequence was repeated at rest ten minutes later using a second bolus of 0.075 mmol/kg contrast agent.A 3D inversion-recovery gradient-echo sequence in short axis views for late gadolinium enhancement (LGE) visualization was acquired ten minutes after the second bolus of contrast agent . The inversion time was individually adjusted for complete nulling of the myocardium.Two experienced readers, blinded to patients’ data and angiographic results, analyzed the anonymized DICOM files. All images were analyzed on a separate workstation . Functional images were analyzed for end-diastolic and end-systolic volumes. Ventricular ejection fractions were calculated, respectively.For evaluation of myocardial perfusion reserve each reader drew the endo- and epicardial left ventricular contours manually in each adenosine and rest perfusion image after correction for motion using the same software  independently from the other reader. The myocardium was divided into 16 segments according to the recommendations of the American Heart Association . The resCoronary angiography was performed within 48 hours after CMR in accordance to the ACC/AHA guidelines . In caset test after being tested for normal distribution by the D’Agostino-Pearson test. They are reported as mean value ± standard deviation. Categorical data is presented as number (%) and compared using the Fisher’s exact test.Continuous variables were tested by the two-tailed Diagnostic accuracies of both readers in comparison to the quantitative coronary angiographic results were tested using receiver-operating characteristics curve analyses.Inter-observer agreement was being tested using Spearman’s coefficient of correlation (ρ). Additionally, the correlation coefficient r was calculated. A p value <0.05 was considered significant for all tests.Six patients had to be excluded due to obesity (N = 3), previous unknown coronary artery bypass surgery N = 1) and uncompleted CMR exam due to technical issues (N = 2). Thus, our study population consisted of 53 patients. Mean age was 63.0 ± 9.3 years; 68% of our patients were male. Patients’ characteristics including cardiovascular risk factors, Framingham 10 years risk for cardiovascular events, history of CAD, and medication are provided in Table  and uncoNo major complications were observed during CMR. The results of the left and right ventricular volumetric analysis are provided in Table In four patients the image quality was insufficient for quantitative perfusion analysis. Latter mentioned patients were excluded from further analysis. In two patients a total of four segments had to be excluded from quantitative perfusion due to interference of the left ventricular outflow tract. Mean myocardial perfusion reserve indices of both readers per perfusion territory are provided in Table Coronary angiography was performed in all patients without major complications. QCA revealed a coronary stenosis ≥70% in 25 (47.2%) patients (see Table Receiver operator characteristic (ROC) analysis of myocardial perfusion reserve quantification of both readers yielded an area under the curve of 0.78 and 0.73 for RCA, 0.66 and 0.69 for LAD, and 0.52 and 0.53 for LCX perfused territories, respectively. There were no significant differences between both readers. ROC curves for all perfusion territories are shown in Figure There is little data about inter-observer agreement of quantitative perfusion assessment at 1.5 Tesla, and this is to the best of our knowledge, the first study to report inter-observer agreement of quantitative myocardial perfusion analysis at 3 Tesla. We were able to demonstrate a high inter-observer agreement of quantitative myocardial perfusion reserve performed at 3 Tesla. The available studies at 1.5 Tesla report an inter-observer agreement of kappa = 0.66 . Other sThe diagnostic accuracy observed in our study showed good values for RCA, reduced accuracy for LAD, and poorer accuracy for LCX perfused myocardial territories. This is in concordance to similar observations with best values for RCA and moderate values for LCX supplied segments . Latter A recent study proved a poor correlation of r = 0.58 between QCA and fractional flow reserve . HoweverPatients who previously had undergone coronary artery bypass or prosthetic valve surgery were excluded from the study. Hence, this might be a limitation because the results of the study at hand might not be translatable to this population of patients.Moreover, we had to exclude four patients from quantitative perfusion analysis because of poor image quality. In two other patients a total of four segments were excluded due to interference of the left ventricular outflow tract. This was done to allow for good and reliable quantitative perfusion analysis. However, this is another possible limitation to our study in terms of selection bias.Quantification of myocardial perfusion reserve at 3 Tesla yields very high inter-observer agreement, as could be shown in the present study. Diagnostic accuracy in comparison to quantitative coronary analysis for the LAD and RCA perfused myocardial territories is good and moderate for the LCX perfused territories.CMR: Cardiovascular magnetic resonance; CAD: Coronary artery disease; QCA: Quantitative coronary angiography; LGE: Late gadolinium enhancement.The authors declare that they have no competing interests.KI analysis and interpretation of data, drafting the manuscript. TW analysis and interpretation of data. LS analysis and interpretation of data. DB analysis and interpretation of data, drafting the manuscript. WR final approval of the manuscript, revising the manuscript critically for important intellectual content. PB conception and design, analysis and interpretation of data, drafting the manuscript. All authors read and approved the final manuscript.


Area at risk (AAR) is an important parameter for the assessment of the salvage area after revascularization in acute myocardial infarction (AMI). By combining AAR assessment by T2-weighted imaging and scar quantification by late gadolinium enhancement imaging cardiovascular magnetic resonance (CMR) offers a promising alternative to the "classical" modality of Tc99m-Sestamibi SPECT. Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury, particularly T1-mapping and T2-mapping, have attracted rising attention. But far no direct comparison between the different sequences in the setting of AMI and a validation against SPECT have been reported.We analyzed 14 patients undergoing primary coronary revascularization in AMI in whom both a pre-intervention Tc99m-Sestamibi-SPECT and CMR imaging at a median of 3.4  days after the acute event were performed. Size of AAR was measured by 4 different non-contrast CMR techniques on corresponding short axis slices: T2-weighted, fat-suppressed turbospin echo sequence (TSE), cine balanced FFE sequences in systolic phase (CINE), T2-mapping from T2-weighted balanced FFE sequences (T2-MAP) and T1-mapping (MOLLI). For each CMR sequence, the AAR was quantified by appropriate methods  and correlated with Tc99m-Sestamibi-SPECT. All measurements were performed on a 1.5 Tesla scanner.The size of the AAR assessed by CMR was 28.7±20.9 % of left ventricular myocardial volume (%LV) for TSE, 15.8±10.3 %LV for CINE, 39.5±16.8 %LV for T2-MAP, and 33.0±14.9 %LV for MOLLI. AAR assessed by SPECT measured 41.6 ±20.7 %LV. Correlation analysis revealed best correlation with SPECT for T2-MAP at a R2-threshold of 62.5 milliseconds , for MOLLI at R1-threshold of 1100 ms , and for TSE at 2 SD above remote . CINE at 2 SD above remote had a similar correlation (r=0.87) but significantly underestimated AAR .For the assessment of area at risk in AMI, the novel T2-mapping technique correlates best with SPECT size, T1-mapping with MOLLI and standard T2-weighted imaging show similar good correlations.none


Diabetes mellitus (DM) is one of the most important risk factors for atrial fibrillation (AF) and is a predictor of stroke and thromboembolism. DM may increase the incidence of AF, and when it is combined with other risk factors, the incidence of stroke and thromboembolism may also be higher; furthermore, hospitalization due to heart failure appears to increase. Maintenance of well-controlled blood glucose and low levels of HbA1c in accordance with guidelines may decrease the incidence of AF. The mechanisms of AF associated with DM are autonomic remodeling, electrical remodeling, structural remodeling, and insulin resistance. Inhibition of the renin-angiotensin system is suggested to be an upstream therapy for this type of AF. Studies have indicated that catheter ablation may be effective for AF associated with DM, restoring sinus rhythm and improving prognosis. Catheter ablation combined with hypoglycemic agents may further increase the rate of maintenance of sinus rhythm and reduce the need for reablation. Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder and contributes to thromboembolism. The presence of AF is an independent risk factor for thromboembolism; especially stroke in association with AF increases mortality and morbidity, leading to greater disability, longer hospital stays, and worse quality of life , 2. TherP < 0.0001). DM is a strong and independent risk factor for the occurrence of AF, with an odds ratio (OR) of 2.13 (P < 0.0001) [P = 0.0031) and a higher risk of developing persistent AF . When patients with new onset DM developed AF, the occurrence of heart failure was much higher  [P < 0.001). After adjusting for multiple risk factors for AF, the RR of AF in patients with DM was still 1.24, and the population-attributable fraction of AF owing to DM was 2.5%. Among 75-year-old patients, occurrence of AF was associated with long-term hyperglycemia, and it was suggested that proactive screening for DM or prediabetes should be performed in patients with a history of AF more than 5 years [AF commonly coexists with cardiovascular risk factors and disorders, which in turn increase the risk of the complications associated with the arrhythmia. The common risk factors for AF are cardiovascular, including hypertension, congestive heart failure, valvular heart disease, and vascular disease. As a cardiovascular risk factor, DM may be associated with the development and progression of AF. Investigators in the VHAH study reported the incidence of AF in patients with DM to be 14.9%, which was significantly higher than that in patients with hypertension but not DM  increase of multivariate-adjusted all-cause mortality in DM patients with AF during the 4.3-year follow-up period compared with those without AF, and cardiovascular mortality, risk of stroke, and heart failure increased significantly . Routine treatment with a fixed combination of perindopril and indapamide reduced blood pressure by 5.3/2.3 mmHg and by 5.9/2.3 mmHg more than placebo in patients with AF, significantly decreasing the risk of cardiovascular events and all-cause mortality. Thus, a comprehensive therapeutic strategy that aggressively targets all cardiovascular risk factors is very important for DM patients with AF [AF is a marker of poor prognosis in patients with DM and increases the risk of cardiovascular events and all-cause mortality. Diabetic neuropathy may mask the cardiac symptoms of first-recorded AF, making it asymptomatic, which may increase the risk of further cardiovascular events and mortality . The ADV with AF .P < 0.0001) [DM was an independent risk factor for the recurrence of AF in patients with persistent AF who underwent successful synchronization with current cardioversion, over a median follow-up period of 74 days. In patients with DM, the sinus rhythm maintenance rate was 45.2%, which was lower than that of patients without DM  . A study 0.0001)  reported 0.0001) .The precise pathophysiologic mechanisms that cause AF in DM patients are unknown . The proCardiac autonomic neuropathy (CAN) is a common complication of DM that significantly increases mortality. Reports of the morbidity from CAN in DM patients are inconsistent, which may be related to variations in the populations studied and the methods used to screen for CAN . The morP < 0.01). Sympathetic stimulation significantly shortened the effective refractory period (ERP) of atrial cells in both groups, but the heterogeneity of the atrial ERP increased in the DM rats only. Parasympathetic stimulation also increased the incidence of AF via shortening of the atrial ERP in both DM rats and controls. Immunohistochemical staining of the right atrium aimed at determining the distribution of sympathetic nerves revealed that tyrosine hydroxylase positive nerves were significantly more heterogeneous in DM rats than in control rats, whereas the heterogeneity of acetylcholine esterase positive nerves did not differ between the two groups. This evidence indicates that cardiac adrenergic nerve stimulation in individuals with DM can lead to AF. The heterogeneity of sympathetic innervation is increased in DM, which suggests that autonomic remodeling may increase susceptibility to AF in this group [The autonomic dysfunction in DM patients can be caused by hyperglycemia-related pathophysiologic pathways such as the formation of advanced glycation end products, elevated oxidative/nitrosative stress with increased production of free radicals, and activation of the polyol and protein kinase C pathway, as well as poly-ADP ribosylation and neuronal damage-associated genes . Most DMis group . Animal DM cardiomyopathy  can lead to left ventricular hypertrophy and increased susceptibility to ischemic injury and the morbidity of heart failure, thereby increasing mortality. Possible pathophysiologic mechanisms of DM cardiomyopathy include myocardial hypertrophy, myocardial lipotoxicity, oxidative stress, cellular apoptosis, interstitial fibrosis, contraction-relaxation dysfunction, impaired myocardial contractile reserve, mitochondrial dysfunction, and disorders of myocardial metabolism . A studyAtrial fibrosis is also an important mechanism for cardiac structural and electrical remodeling. In a DM rat model, there are widespread fibrotic deposits in the atria that are prone to the formation of anchoring points for reentry circuits and changes in the forward propagation of fibrillatory wavelets and thus cause atrial fractionated potentials and conduction delay . OxidatiPrevious studies have demonstrated that patients with insulin-dependent DM suffer AF attacks while hypoglycemic. Some experts consider the cause of such AF attacks to be fluctuations in glycemia rather than the hyperglycemic state itself . A study2 scoring system. The European Society of Cardiology Guidelines for the Management of Atrial Fibrillation (2010 ESC) recommended the use of a more appropriate system, the CHA2DS2-VASc. In AF patients with DM, if the risk of major bleeding is low or the benefit/risk ratio is considered high, an oral anticoagulant such as a vitamin K antagonist (VKAs) is the first choice independent of rate control or rhythm control. The dose of VKAs depends on the target intensity INR  of 2.0–3.0, with a target value of 2.5. New anticoagulants  are alternatives to VKAs [AF is a major risk factor for stroke and thromboembolism. The mortality, disability rate, and risk of stroke recurrence are all higher in stroke caused by AF than in that due to other causes. The risk of stroke varies among DM patients with AF, and treatment relies on risk evaluation and appropriate anticoagulation therapy. The simplest way to assess the risk of stroke is the CHADS to VKAs .Atrial structural remodeling or fibrosis can decrease the conduction speed of the atrial myocardium, which may be the underlying mechanism of DM-related AF. Angiotensin II receptor blockers (ARBs) may play an important role in the upstream therapy of AF through the following mechanisms: decreasing atrial fibrosis and delaying atrial structural remodeling; inhibiting the production and facilitating the degradation of collagen fibers, thereby decreasing the left atrial overload that is the major reason for the development and progression of AF ; modifyiγ activator, may potentially benefit for AF prevention [Several studies indicated thiazolidinedione as a class of peroxisome proliferator-activated receptor-evention –42, espeevention –47. The evention .β-blockers, nondihydropyridine calcium channel blockers, and digitalis glycosides. Drugs commonly used to control heart rhythm are amiodarone and dronedarone. After treatment with the full dose of an antiarrhythmic drug, catheter ablation may be of further benefit in the treatment of AF [P = 0.24). The possibility of an episode of asymptomatic AF caused by DM neuropathy cannot be excluded in this study, so the success rate of the AF ablation may have been overestimated. This study also suggested that the incidence of procedure-associated complications was higher in the DM patients . The major complications were hemorrhage and thromboembolism. When hemorrhage was excluded, the incidence of complications was 6.4%. There was an increased tendency to develop cardiac tamponade and thromboembolism in the DM patients; possible reasons include the following: AF is a risk factor for cerebral embolism; DM can cause both prothrombotic and proinflammatory states; and hyperinsulinemia can induce a prothrombotic state that is closely related to metabolic disorders  involving platelets, the coagulation cascade, and fibrinolysis [P = 0.001). The Life Quality Scale score was significantly higher in the ablation group than in the drug group; 17.1% of patients developed obvious drug-associated side effects, and the hospitalization rate was significantly higher in the drug treatment group (P = 0.01). The major complication of catheter ablation was puncturing site bleeding. This evidence suggests that catheter ablation can significantly improve the prognosis of DM patients with AF compared with drug treatment alone [P = 0.02), it still reached 18.5%, which may be associated with intra-atrial conduction delay and decreased voltage [Antiarrhythmic treatment in AF patients includes rate control and rhythm control; the choice of drug should be individualized. Commonly used antiarrhythmic drugs that control heart rate in AF patients are nt of AF . A largeinolysis . Anothernt alone . Assessm voltage .P = 0.03) and the proportion that underwent a second ablation was lower  among patients treated with pioglitazone. This evidence indicates that, in T2DM with paroxysmal AF, pioglitazone can significantly increase the success rate of catheter ablation and decrease the recurrence of AF. Left atrial size is associated with recurrence of atrial arrhythmia, which can be decreased by both pioglitazone and ARBs [Pioglitazone is a commonly prescribed drug in clinical practice with anti-inflammatory and antioxidative effects. In a contrast study, 150 selected T2DM patients with paroxysmal AF were divided into two groups depending on whether pioglitazone was given after catheter ablation. Antiarrhythmic drugs were discontinued in patients who remained in sinus rhythm. After an average 15-month followup, compared with the control group, the rate of maintenance of sinus rhythm was higher (86.3% versus 70.7%, and ARBs .DM is one of the most important risk factors for the development and progression of AF and can predict the occurrence of stroke and thromboembolism. Long-term anticoagulation therapy with VKAs is recommended in AF patients with DM. DM can increase the incidence of AF, and when it is combined with other risk factors, the incidence of stroke and thromboembolism may be even higher. The incidence and rate of hospitalization due to heart failure may be increased. Maintenance of well-controlled blood glucose and low HbA1c according to guidelines may decrease the incidence of AF. The mechanisms of AF associated with DM are autonomic remodeling, electrical remodeling, structural remodeling, and insulin resistance; there are few studies concerning the role of inflammation and oxidative stress in the pathogenesis of AF. Inhibition of the renin-angiotensin system is expected to be an upstream therapy for this type of AF. Some studies have indicated that catheter ablation may be effective in AF associated with DM, restoring sinus rhythm and improving prognosis. Catheter ablation combined with hypoglycemic agents may further increase the rate of maintenance of sinus rhythm and also reduce the risk of need for reablation.


MRI is the accepted gold standard for assessment of left ventricular systolic function; however, no standards are available to assess diastolic function at MRI. E/A and E/e’ ratios are currently used in echocardiography to evaluate left ventricular diastolic function. Measuring these ratios with phase contrast MRI may provide a complementary approach to assessing left ventricular function.To validate E/A and E/e’ ratios acquired with phase contrast MRI relative to established values using echocardiography.17 self-reported healthy volunteers were recruited under an IRB approved protocol. Ultra fast phase contrast data was acquired on a 1.5T Siemens Aera using both breath-hold (30 frames per cardiac cycle) and free breathing (50 frames per cardiac cycle) paradigms. To measure e’ velocities, phase contrast data (Venc 25cm/s) was acquired in the short axis orientation at a slice position where the myocardium on the apical side of the valve ring was within the slice throughout the cardiac cycle. To measure E and A velocities, phase contrast data (Venc 80 cm/s) was acquired in a single slice parallel to the mitral valve annulus, positioned such that the slice stayed below the valve throughout the entire cardiac cycle. E and A velocities as well as septal and lateral e’ velocities were calculated using standard flow post-processing. 2 subjects were excluded from both analyses due to improper gating, and 4 additional subjects were excluded from the breath hold analysis because there was too much noise to identify e’ velocities.With free breathing, E/A was measured at 1.7 ± 0.5 (range 0.8-2.6), septum E/e’ was measured at 5.4 ± 1.5 (range 2.5-7.4), and lateral E/e’ ratio was measured at 5.1 ± 1.7 (range 2.6-8.4). With the breath hold, E/A was measured at 1.5 ± 0.6 (range 0.7-2.7), septum E/e’ was measured at 6.1 ± 2.2 (range 3.6-10.2), and lateral E/e’ was measured at 5.4 ± 2.1 (range 3.5-10.9). Subjects with an E/e’ ratio above 8.0 had normal left atrial size. Figure The measured E/A and E/e’ values are within normal limits using cutoff values that have been published with echocardiography , suggest