Background: The size and composition of commercially available ultrasonic contrast microbubbles a... more Background: The size and composition of commercially available ultrasonic contrast microbubbles are such that when insonated at routinely used diagnostic frequencies (2-7MHz), the bubbles resonate and strongly scatter ultrasound. Recently there has been increasing interest in imaging and manipulating these microbubbles at higher frequencies (30-40MHz) for possible applications in targeting microbubble-encapsulated drugs to specific plaque sites in arteries and to image such sites using intravascular ultrasound. Due to commercial sensitivity re shell constitutents and manufacture, targeting of specific commercial agents was not possible. Aim: To produce an ultrasonic contrast microbubble capable of resonating at 30-40MHz and to investigate the possibility of using such an agent for targeting specific cell-lines found in the arterial wall. Method: A lipid-encapsulated nitrogen-filled microbubble was developed in-house. The agent was diluted to various concentrations using saline and blood-mimicking fluid (BMF). Using a ClearView Ultra system, an Atlantis SR intravascular probe was inserted into each solution and one frame of unprocessed ultrasonic data was acquired. The data was downloaded onto a PC. A region-of-interest (ROI) of 128 data points and 9 ultrasonic lines was chosen. Over these ROIs, mean backscatter power was calculated and referenced to data collected from a waterair interface. The ability of the agent to be targeted to specific cells was assessed microscopically by labelling the microbubbles with an antibody (CD54) and then passing these microbubbles over endothelial cells grown on an agar interface. A flow chamber was developed to enable both acoustical and optical images to be obtained of the cells under physiological flow conditions. Results: At concentrations of 25mg/ml, mean backscatter power was approximately 9dB less than a commercially available agent (Definity). This level of backscatter is adequate for arterial plaque studies. Further development is underway to increase the scattering cross-section of the bubbles. When observed using a microscope and in the flow chamber, antibody-loaded microbubbles were observed firmly attached to cells. Conclusions: This technique has the potential to identify those plaques which are disrupted or recently eroded and for which diagnostic techniques have limitations. 187 Parameters influencing the myocardial delivery of nanoparticles using ultrasound-targeted microbubble destruction.
Background: Data regarding the influence of different levels of renal dysfunction on clinical and... more Background: Data regarding the influence of different levels of renal dysfunction on clinical and echocardiographic results of MitraClip therapy are scarce. We aimed to evaluate the impact of baseline advance renal failure in the outcomes of a cohort of patients treated with MitraClip. Methods and results: We analyzed data from a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012. Patients were classified as advanced chronic kidney disease (CKD, creatinine clearance [CrCl] b30 ml/min, group 1, n = 20), moderate CKD (CrCl 30-60 ml/min, group 2, n = 78) and normal renal function (CrCl N 60 ml/min, group 3, n = 75). Twenty patients (11.5%) presented advanced CKD. Procedural success was equal in the 3 groups (95.0% group 1, 100% in group 2 and 96.0% in group 3, p = 0.180). Post-procedural MR and NYHA class at 1 month (MR ≥ 3 + 5.0% vs. 0% vs. 4.0% p = 0.190 and NYHA N II 40.0% vs. 21.0% vs. 18.3%, p = 0.101) and 6 months (MR ≥ 3 + 0% vs. 13.0% vs. 2.7%, p = 0.330; and NYHA class N II 54.5% vs. 26.9% vs. 25.6%, p = 0.298) did not differ between groups. However, patients in group 1 experienced higher frequency of the composite end-point of mortality or readmission at 16.2 ± 11.1 months of follow-up (HR 4.8, CI 95% 1.1-21.3). Conclusion: Advanced CKD is linked to an excess of cardiac adverse events. This should be judiciously taken into account when selecting patients for MitraClip.
ABSTRACT Ekokardiografi och mobil myokardskintigrafi är lätta att använda vid sängkanten på akut-... more ABSTRACT Ekokardiografi och mobil myokardskintigrafi är lätta att använda vid sängkanten på akut- och infarktvårdavdelning och kan styra patientflödet. Akut myokardischemi kan påvisas som nedsatt regional väggrörlighet och/eller perfusion med både ekokardiigrafi och ektomografi. Kvantitativ myokardrörlighetsanalys underlättar och minskar subjektiviteten i ischemidiagnostiken.
European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology, 2009
Colour tissue Doppler (TD) has been reported to underestimate the longitudinal myocardial motion ... more Colour tissue Doppler (TD) has been reported to underestimate the longitudinal myocardial motion velocities measured with spectral TD. This study evaluates the effect of temporal smoothing and offline gain settings on the results of velocity measurements with these two methods and the difference between them. In 57 patients, 2D data and left ventricular velocity profiles were acquired using spectral and colour TD for a subsequent offline analysis. Longitudinal myocardial velocities were measured at unsaturated, 50%-saturated and fully saturated gain, and before and after temporal smoothing using 30, 50, and 70 ms filters, respectively. Gain level and filter width altered significantly the measured velocities. Peak systolic and early diastolic velocities were significantly higher (P < 0.001) and E/E' ratio was significantly lower (P < 0.001) with spectral TD than with colour TD, although there was a good correlation between the results of both TD modalities. The differences...
Background: Echocardiography is a well-established tool for risk stratification in patients with ... more Background: Echocardiography is a well-established tool for risk stratification in patients with acute coronary syndrome (ACS). ACS has significant impact on LV dyssynchrony, and detrimental effects on systolic function and long term outcome. The aims of this study were to determine whether LV dyssynchrony carries any predictive information in an unselected ACS population and to evaluate if it has any incremental value to the information given from conventional echocardiographic measurements. Methods: The study included 227 consecutive ACS patients. Primary endpoint was the composite of death, new MI, or rehospitalisation due to heart failure. Dyssynchrony was measured as intersegmental variation of time to peak strain, the post systolic index (PSI) and myocardial performance index (MPI) with the standard deviation and difference between lowest and highest value (delta) expressing the amount of dyssynchrony. Septal-lateral delay was also tested. All dyssynchrony parameters were compared with Ejection fraction (EF). Results: The median follow up time was 53 months. 85 patients reached the combined endpoint. Patients with and without a subsequent combined endpoint differed significantly regarding calculated SD: s and delta-value for PSI, time to peak 2D-strain and MPI but not regarding septal-lateral delay. In ROC-analysis none of the dyssynchrony parameters had larger AUC than EF. When adjusting for traditional risk factors none of the dyssynchrony parameters remained associated with outcome, whereas EF still did. Conclusion: LV dyssynchrony seem to have significant prognostic information in patient with acute coronary syndrome but in comparison to conventional parameters such as EF there is no incremental value of this information.
Journal of the American Society of Echocardiography, 2010
Background: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and ... more Background: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing. Methods: Forty-three male participants in a 30-km crosscountry race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T s-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling. Results: Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 mg/L; interquartile range [IQR], 0.01-0.04 mg/L) than in repeat runners (median, 0.01 mg/L; IQR, 0.01-0.02 mg/L) (P = .03). Although new and repeat runners had similar T s-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P < .05 for all). Conclusion: Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.
The International Journal of Cardiovascular Imaging formerly The International Journal of Cardiac Imaging, 2004
Background: The early diastolic downward slope (EDS) of the left atrioventricular plane displacem... more Background: The early diastolic downward slope (EDS) of the left atrioventricular plane displacement (AVPD) is a parameter of early left ventricular (LV) diastolic filling, particularly useful in revealing pseudonormalisation of the transmitral Doppler early to atrial (E/A) ratio. In recent studies LV early diastolic function seems to be closely linked to LV systolic function. In order to further examine this relationship we studied the correlation between EDS and traditional Doppler parameters of LV diastolic function as well as between EDS and systolic parameters. Methods: LV diastolic function was assessed by echocardiography/Doppler in 62 consecutive patients by measurement of EDS and using a traditional fourgrade scale based on a combination of the E/A ratio, the E-wave deceleration time (Edt), and the systolic/ diastolic ratio of the pulmonary venous inflow (S/D). LV systolic function was evaluated by ejection fraction (LVEF) and AVPD. EDS was assessed from AVPD registrations. Results: In univariate analysis of variance (ANOVA), EDS was not significantly related to overall diastolic function, but highly significantly related to both LVEF (p ¼ 0.001) and AVPD (p < 0.0001). Conclusions: EDS was more closely related to LV systolic parameters than to LV diastolic function assessed traditionally by Doppler, using a combination of E/A, Edt and S/D. This relationship between the early filling of the LV and the LV systolic function is in line with some earlier findings. It is suggestive of a relationship between the systolic and early diastolic performance of the LV.
Background Simpson ejection fraction(Simpson-EF), wall motion score index (WMSI), atrioventricula... more Background Simpson ejection fraction(Simpson-EF), wall motion score index (WMSI), atrioventricular (AV) plane displacement (AVPD) and fractional shortening (FS) are all established formal echocardiographic methods for the assessment of left ventricular (LV) systolic function. Visually estimated (eyeballing) EF ejection fraction may be considered somewhat more subjective, although shown to correlate well with radionuclide ventriculography. We aimed to explore if echocardiographic eyeballing-EFeyeballing ejection fraction is comparable to formal methods for the evaluation of LV left ventricular systolic function. Methods We assessed 89 consecutive patients after myocardial infarction (n=54) or before coronary angiography (n=35). Eyeballing-EFEyeballing ejection fraction and WMSI wall motion score index were evaluated in the long-axis, short-axis and apical 4-and 2-chamber views. Simpson-EF ejection fraction and AV plane displacement were assessed in the apical views. Fractional Sshortening was measured in the parasternal long-axis view. The respective systolic function measurements were in each patient made at different time points by a single investigator, masked to prior results. Results All formal methods correlated significantly with eyeballing-EF eyeballing ejection fraction (p<0.
BACKGROUND Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker rel... more BACKGROUND Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker release and impaired myocardial function. The impact on ventricular electrophysiology is largely unknown. OBJECTIVE The objective of this study was to examine changes in ventricular repolarization after a 30-km crosscountry race in runners aged Ն55 years. METHODS Fifteen healthy participants (62 Ϯ 5 years) were assessed using biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], troponin T [TnT]), tissue Doppler echocardiography, and vectorcardiography at baseline, within 1 hour postrace and on days 1 and 6 postrace. RESULTS During the race, NT-proBNP increased from 42 ng/L (interquartile range 25-117) to 187 ng/L (113-464), and TnT increased from undetectable levels to 0.03 g/L (0.015-0.05). Global strain (19.1% Ϯ 2.2%) decreased on day 1 (17.2% Ϯ 1.8%) and day 6 (17.9% Ϯ 1.5%; P Ͻ.01). QT c increased from 431 Ϯ 15 ms prerace to 445 Ϯ 22 ms postrace and 445 Ϯ 15 ms on day 1 (P Ͻ.05), mainly because of an increased T peak-end interval (prerace 108 Ϯ 13 ms, postrace 127 Ϯ 43 ms, day 1 127 Ϯ 43 ms; P Ͻ.05). Postrace, T area (baseline 75 Ϯ 26 Vs) peaked on day 1 (105 Ϯ 42 Vs) and remained high on day 6 (89 Ϯ 37 Vs; P Ͻ.05). Runners with higher baseline NT-proBNP developed greater impairment of myocardial velocities (rho ϭ Ϫ0.68 to Ϫ0.54; P Ͻ.05) and a larger increase in T area (rho ϭ 0.73; P Ͻ.01). CONCLUSION Cardiac fatigue induced by prolonged exertion is associated with sustained abnormalities in ventricular repolarization. Runners with higher baseline NT-proBNP are especially liable to such alterations of cardiac function.
European Journal of Cardiovascular Prevention & Rehabilitation, 2007
There is growing evidence that erectile dysfunction is a sentinel for future coronary artery dise... more There is growing evidence that erectile dysfunction is a sentinel for future coronary artery disease. Recently published studies have shown signs of impaired coronary endothelial function in patients with erectile dysfunction, without clinical cardiovascular disease and diabetes. We evaluated the magnitude of coronary vasodilatory dysfunction in men with erectile dysfunction, as compared with men with impaired glucose metabolism (impaired fasting glucose or diabetes) and healthy controls. We investigated men aged 68-73 years with erectile dysfunction (n=12), age-matched men with impaired glucose metabolism, who all proved to have erectile dysfunction (n=15), and age-matched male controls (n=12). Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve in the left anterior descending artery was examined using Doppler ultrasound and intravenous adenosine provocation. Coronary flow velocities at rest did not differ between the three groups, but maximum coronary flow velocity was significantly lower in the erectile dysfunction group (P=0.004) and in the impaired glucose metabolism group (P=0.019), as compared with controls. There was no difference between the erectile dysfunction and impaired glucose metabolism groups. Coronary flow velocity reserve was reduced in the erectile dysfunction group (P=0.026) compared to controls, but was similar compared to the impaired glucose metabolism group. In multivariate analysis including all groups, erectile dysfunction score was the only independent predictor of reduced coronary flow velocity reserve (P=0.020). The magnitude of early coronary endothelial and smooth muscle cell dysfunction in otherwise healthy men with erectile dysfunction was comparable to that of patients with impaired glucose metabolism: a well known risk factor for coronary artery disease.
Background: The use of two-dimensional echocardiography (2D echo) for detection of ischaemia is l... more Background: The use of two-dimensional echocardiography (2D echo) for detection of ischaemia is limited due to high user dependency. Longitudinal motion is sensitive for ischaemia and usable for quantitative measurement of longitudinal myocardial function but time consuming. Velocity tracking (VeT) is a new method that gives an easy three-dimensional understanding of both systolic and diastolic regional motion, using colour coded bullÕs eye presentation of longitudinal velocity, derived from colour coded tissue Doppler. The aim of this study was to test the accuracy of VeT in detecting ischaemia in non-ST-segment elevation myocardial infarction (NSTEMI) patients bedside. Methods: Twenty patients with NSTEMI and 10 controls were included. Echocardiography was performed within 24 h of symptoms and prior to coronary angiography. BullÕs eye plots presenting the peak systolic velocity (PSV) and the sum of PSV and the E-wave-velocity (PSV+E) were created using our developed software. VeT was compared to expert wall motion scoring (WMS) and bedside echo. We used the clinical conclusion based on ECG, angiography and clinical picture as Ôgold standardÕ. Results: Sensitivity for ischaemia with VeT (PSV+E) was 85% and specificity 60%. The corresponding sensitivities for expert WMS were 75% (specificity 40%). For regional analysis VeT and WMS showed comparable results with correct regional outcome in 11⁄20 of patients both superior to bedside echo. Conclusion: Velocity tracking is a promising technique that provides an easily understandable three-dimensional bullÕs eye plot for assessment of regional left ventricular longitudinal velocity with great potential for detection of regional dysfunction and myocardial ischaemia.
Background: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visu... more Background: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast Ò software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (b) and myocardial blood flow (Axb) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast Ò-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. Methods: Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue Ò infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast Ò-generated A, b and Axb images, at different time points during rest and stress, were blindly compared to SPECT. Results: We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, b and Axb image interpretation significantly identified ischaemia in all territories (area under the curve 0AE66-0AE80, P = 0AE001-0AE05). Combined A, b and Axb image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0AE63; P<0AE001. Conclusion: Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast Ò-generated images, especially by combined A, b and Axb image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.
Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scint... more Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scintigraphy for the detection of myocardial ischaemia in patients with stable coronary artery disease."
Studies seeking to validate real-time three-dimensional echocardiography (3DE) with regard to car... more Studies seeking to validate real-time three-dimensional echocardiography (3DE) with regard to cardiac function and dimensions have almost exclusively used apical views. However, it has never been examined whether apical views are preferable to parasternal or subcostal views. In the present study, we compared the feasibility of 3DE volumetric measurements of the four heart chambers in three different views. We included 40 patients planned for a routine two-dimensional transthoracic echocardiography examination (2DE). All patients were scanned with both 2DE and 3DE (Sonos 7500; Philips Medical Systems Andover, MA, USA). Parasternal, apical and subcostal views were used for 3DE. Volumes were calculated using manual tracing in 16 planes. 2DE was performed in parasternal longaxis, subcostal and apical four-and two-chamber views. Manual tracing was used for area calculations. To be judged fully traceable, 5⁄6 (85%) or more of the ventricular and atrial walls had to be adequately visualized in each plane. The left ventricle and left atrium were adequately visualized in the 3DE apical view in 34 (85%) and 40 (100%) patients, respectively. Visualization of the right atrium was adequate in 31 (78%) patients, whereas the right ventricle was adequately visualized in only 12 (30%) patients. The apical view of 3DE provided superior visualization of all four heart chambers compared with the parasternal and subcostal views, when applying a slight off-axis approach for both ventricles when needed. Thus, in the present study, there was no incremental value of assessment of chamber volumes in the parasternal and subcostal views.
Background Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stres... more Background Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia. Methods Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue® infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest. Results In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR...
Background: Cardiac time intervals have been described as a measure of cardiac performance, where... more Background: Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements. Methods: We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter-and intraventricular function of the heart by displaying the cardiac phases. Results: The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods. Conclusion: The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.
Background: Traditional echocardiographic methods like left ventricular ejection fraction(EF) and... more Background: Traditional echocardiographic methods like left ventricular ejection fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking (ST) based 2D strain carry important prognostic information in acute coronary syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its high time resolution, may further increase the prognostic value. Peak systolic velocity (PSV) of the basal segments of the left ventricle from TDI is a robust and user independent parameter. The aim was to investigate the prognostic value of PSV compared to EF, WMS, 2D strain and E/e'. Methods: Echocardiographic images were collected and post processed in 227 ACS patients. Additional clinical data was prospectively gathered and patients were followed for 3-5 years regarding the combined endpoint of death or re-admission due to ACS or heart failure. Results: The combined endpoint occurred in 85 (37%) patients. Those with an event had lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p<0.001). In a ROC analysis, the AUC was larger for PSV (0.75) than for EF (0.68), WMS (0.63), 2D strain (0.67) and E/e'(0.70). The combined endpoint increased with decreasing PSV. When adjusting for differences in baseline characteristics in a COX-regression model, PSV remained independently associated with outcome where the others did not. PSV was also less sensitive to image quality with fewer values missing or unacceptable for analysis. Conclusion: Peak systolic velocity (PSV) is a robust measurement that seems to have a strong and independent association with outcome compared to traditional echocardiographic measurements in ACS patients.
Background: The size and composition of commercially available ultrasonic contrast microbubbles a... more Background: The size and composition of commercially available ultrasonic contrast microbubbles are such that when insonated at routinely used diagnostic frequencies (2-7MHz), the bubbles resonate and strongly scatter ultrasound. Recently there has been increasing interest in imaging and manipulating these microbubbles at higher frequencies (30-40MHz) for possible applications in targeting microbubble-encapsulated drugs to specific plaque sites in arteries and to image such sites using intravascular ultrasound. Due to commercial sensitivity re shell constitutents and manufacture, targeting of specific commercial agents was not possible. Aim: To produce an ultrasonic contrast microbubble capable of resonating at 30-40MHz and to investigate the possibility of using such an agent for targeting specific cell-lines found in the arterial wall. Method: A lipid-encapsulated nitrogen-filled microbubble was developed in-house. The agent was diluted to various concentrations using saline and blood-mimicking fluid (BMF). Using a ClearView Ultra system, an Atlantis SR intravascular probe was inserted into each solution and one frame of unprocessed ultrasonic data was acquired. The data was downloaded onto a PC. A region-of-interest (ROI) of 128 data points and 9 ultrasonic lines was chosen. Over these ROIs, mean backscatter power was calculated and referenced to data collected from a waterair interface. The ability of the agent to be targeted to specific cells was assessed microscopically by labelling the microbubbles with an antibody (CD54) and then passing these microbubbles over endothelial cells grown on an agar interface. A flow chamber was developed to enable both acoustical and optical images to be obtained of the cells under physiological flow conditions. Results: At concentrations of 25mg/ml, mean backscatter power was approximately 9dB less than a commercially available agent (Definity). This level of backscatter is adequate for arterial plaque studies. Further development is underway to increase the scattering cross-section of the bubbles. When observed using a microscope and in the flow chamber, antibody-loaded microbubbles were observed firmly attached to cells. Conclusions: This technique has the potential to identify those plaques which are disrupted or recently eroded and for which diagnostic techniques have limitations. 187 Parameters influencing the myocardial delivery of nanoparticles using ultrasound-targeted microbubble destruction.
Background: Data regarding the influence of different levels of renal dysfunction on clinical and... more Background: Data regarding the influence of different levels of renal dysfunction on clinical and echocardiographic results of MitraClip therapy are scarce. We aimed to evaluate the impact of baseline advance renal failure in the outcomes of a cohort of patients treated with MitraClip. Methods and results: We analyzed data from a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012. Patients were classified as advanced chronic kidney disease (CKD, creatinine clearance [CrCl] b30 ml/min, group 1, n = 20), moderate CKD (CrCl 30-60 ml/min, group 2, n = 78) and normal renal function (CrCl N 60 ml/min, group 3, n = 75). Twenty patients (11.5%) presented advanced CKD. Procedural success was equal in the 3 groups (95.0% group 1, 100% in group 2 and 96.0% in group 3, p = 0.180). Post-procedural MR and NYHA class at 1 month (MR ≥ 3 + 5.0% vs. 0% vs. 4.0% p = 0.190 and NYHA N II 40.0% vs. 21.0% vs. 18.3%, p = 0.101) and 6 months (MR ≥ 3 + 0% vs. 13.0% vs. 2.7%, p = 0.330; and NYHA class N II 54.5% vs. 26.9% vs. 25.6%, p = 0.298) did not differ between groups. However, patients in group 1 experienced higher frequency of the composite end-point of mortality or readmission at 16.2 ± 11.1 months of follow-up (HR 4.8, CI 95% 1.1-21.3). Conclusion: Advanced CKD is linked to an excess of cardiac adverse events. This should be judiciously taken into account when selecting patients for MitraClip.
ABSTRACT Ekokardiografi och mobil myokardskintigrafi är lätta att använda vid sängkanten på akut-... more ABSTRACT Ekokardiografi och mobil myokardskintigrafi är lätta att använda vid sängkanten på akut- och infarktvårdavdelning och kan styra patientflödet. Akut myokardischemi kan påvisas som nedsatt regional väggrörlighet och/eller perfusion med både ekokardiigrafi och ektomografi. Kvantitativ myokardrörlighetsanalys underlättar och minskar subjektiviteten i ischemidiagnostiken.
European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology, 2009
Colour tissue Doppler (TD) has been reported to underestimate the longitudinal myocardial motion ... more Colour tissue Doppler (TD) has been reported to underestimate the longitudinal myocardial motion velocities measured with spectral TD. This study evaluates the effect of temporal smoothing and offline gain settings on the results of velocity measurements with these two methods and the difference between them. In 57 patients, 2D data and left ventricular velocity profiles were acquired using spectral and colour TD for a subsequent offline analysis. Longitudinal myocardial velocities were measured at unsaturated, 50%-saturated and fully saturated gain, and before and after temporal smoothing using 30, 50, and 70 ms filters, respectively. Gain level and filter width altered significantly the measured velocities. Peak systolic and early diastolic velocities were significantly higher (P < 0.001) and E/E' ratio was significantly lower (P < 0.001) with spectral TD than with colour TD, although there was a good correlation between the results of both TD modalities. The differences...
Background: Echocardiography is a well-established tool for risk stratification in patients with ... more Background: Echocardiography is a well-established tool for risk stratification in patients with acute coronary syndrome (ACS). ACS has significant impact on LV dyssynchrony, and detrimental effects on systolic function and long term outcome. The aims of this study were to determine whether LV dyssynchrony carries any predictive information in an unselected ACS population and to evaluate if it has any incremental value to the information given from conventional echocardiographic measurements. Methods: The study included 227 consecutive ACS patients. Primary endpoint was the composite of death, new MI, or rehospitalisation due to heart failure. Dyssynchrony was measured as intersegmental variation of time to peak strain, the post systolic index (PSI) and myocardial performance index (MPI) with the standard deviation and difference between lowest and highest value (delta) expressing the amount of dyssynchrony. Septal-lateral delay was also tested. All dyssynchrony parameters were compared with Ejection fraction (EF). Results: The median follow up time was 53 months. 85 patients reached the combined endpoint. Patients with and without a subsequent combined endpoint differed significantly regarding calculated SD: s and delta-value for PSI, time to peak 2D-strain and MPI but not regarding septal-lateral delay. In ROC-analysis none of the dyssynchrony parameters had larger AUC than EF. When adjusting for traditional risk factors none of the dyssynchrony parameters remained associated with outcome, whereas EF still did. Conclusion: LV dyssynchrony seem to have significant prognostic information in patient with acute coronary syndrome but in comparison to conventional parameters such as EF there is no incremental value of this information.
Journal of the American Society of Echocardiography, 2010
Background: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and ... more Background: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing. Methods: Forty-three male participants in a 30-km crosscountry race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T s-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling. Results: Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 mg/L; interquartile range [IQR], 0.01-0.04 mg/L) than in repeat runners (median, 0.01 mg/L; IQR, 0.01-0.02 mg/L) (P = .03). Although new and repeat runners had similar T s-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P < .05 for all). Conclusion: Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.
The International Journal of Cardiovascular Imaging formerly The International Journal of Cardiac Imaging, 2004
Background: The early diastolic downward slope (EDS) of the left atrioventricular plane displacem... more Background: The early diastolic downward slope (EDS) of the left atrioventricular plane displacement (AVPD) is a parameter of early left ventricular (LV) diastolic filling, particularly useful in revealing pseudonormalisation of the transmitral Doppler early to atrial (E/A) ratio. In recent studies LV early diastolic function seems to be closely linked to LV systolic function. In order to further examine this relationship we studied the correlation between EDS and traditional Doppler parameters of LV diastolic function as well as between EDS and systolic parameters. Methods: LV diastolic function was assessed by echocardiography/Doppler in 62 consecutive patients by measurement of EDS and using a traditional fourgrade scale based on a combination of the E/A ratio, the E-wave deceleration time (Edt), and the systolic/ diastolic ratio of the pulmonary venous inflow (S/D). LV systolic function was evaluated by ejection fraction (LVEF) and AVPD. EDS was assessed from AVPD registrations. Results: In univariate analysis of variance (ANOVA), EDS was not significantly related to overall diastolic function, but highly significantly related to both LVEF (p ¼ 0.001) and AVPD (p < 0.0001). Conclusions: EDS was more closely related to LV systolic parameters than to LV diastolic function assessed traditionally by Doppler, using a combination of E/A, Edt and S/D. This relationship between the early filling of the LV and the LV systolic function is in line with some earlier findings. It is suggestive of a relationship between the systolic and early diastolic performance of the LV.
Background Simpson ejection fraction(Simpson-EF), wall motion score index (WMSI), atrioventricula... more Background Simpson ejection fraction(Simpson-EF), wall motion score index (WMSI), atrioventricular (AV) plane displacement (AVPD) and fractional shortening (FS) are all established formal echocardiographic methods for the assessment of left ventricular (LV) systolic function. Visually estimated (eyeballing) EF ejection fraction may be considered somewhat more subjective, although shown to correlate well with radionuclide ventriculography. We aimed to explore if echocardiographic eyeballing-EFeyeballing ejection fraction is comparable to formal methods for the evaluation of LV left ventricular systolic function. Methods We assessed 89 consecutive patients after myocardial infarction (n=54) or before coronary angiography (n=35). Eyeballing-EFEyeballing ejection fraction and WMSI wall motion score index were evaluated in the long-axis, short-axis and apical 4-and 2-chamber views. Simpson-EF ejection fraction and AV plane displacement were assessed in the apical views. Fractional Sshortening was measured in the parasternal long-axis view. The respective systolic function measurements were in each patient made at different time points by a single investigator, masked to prior results. Results All formal methods correlated significantly with eyeballing-EF eyeballing ejection fraction (p<0.
BACKGROUND Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker rel... more BACKGROUND Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker release and impaired myocardial function. The impact on ventricular electrophysiology is largely unknown. OBJECTIVE The objective of this study was to examine changes in ventricular repolarization after a 30-km crosscountry race in runners aged Ն55 years. METHODS Fifteen healthy participants (62 Ϯ 5 years) were assessed using biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], troponin T [TnT]), tissue Doppler echocardiography, and vectorcardiography at baseline, within 1 hour postrace and on days 1 and 6 postrace. RESULTS During the race, NT-proBNP increased from 42 ng/L (interquartile range 25-117) to 187 ng/L (113-464), and TnT increased from undetectable levels to 0.03 g/L (0.015-0.05). Global strain (19.1% Ϯ 2.2%) decreased on day 1 (17.2% Ϯ 1.8%) and day 6 (17.9% Ϯ 1.5%; P Ͻ.01). QT c increased from 431 Ϯ 15 ms prerace to 445 Ϯ 22 ms postrace and 445 Ϯ 15 ms on day 1 (P Ͻ.05), mainly because of an increased T peak-end interval (prerace 108 Ϯ 13 ms, postrace 127 Ϯ 43 ms, day 1 127 Ϯ 43 ms; P Ͻ.05). Postrace, T area (baseline 75 Ϯ 26 Vs) peaked on day 1 (105 Ϯ 42 Vs) and remained high on day 6 (89 Ϯ 37 Vs; P Ͻ.05). Runners with higher baseline NT-proBNP developed greater impairment of myocardial velocities (rho ϭ Ϫ0.68 to Ϫ0.54; P Ͻ.05) and a larger increase in T area (rho ϭ 0.73; P Ͻ.01). CONCLUSION Cardiac fatigue induced by prolonged exertion is associated with sustained abnormalities in ventricular repolarization. Runners with higher baseline NT-proBNP are especially liable to such alterations of cardiac function.
European Journal of Cardiovascular Prevention & Rehabilitation, 2007
There is growing evidence that erectile dysfunction is a sentinel for future coronary artery dise... more There is growing evidence that erectile dysfunction is a sentinel for future coronary artery disease. Recently published studies have shown signs of impaired coronary endothelial function in patients with erectile dysfunction, without clinical cardiovascular disease and diabetes. We evaluated the magnitude of coronary vasodilatory dysfunction in men with erectile dysfunction, as compared with men with impaired glucose metabolism (impaired fasting glucose or diabetes) and healthy controls. We investigated men aged 68-73 years with erectile dysfunction (n=12), age-matched men with impaired glucose metabolism, who all proved to have erectile dysfunction (n=15), and age-matched male controls (n=12). Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve in the left anterior descending artery was examined using Doppler ultrasound and intravenous adenosine provocation. Coronary flow velocities at rest did not differ between the three groups, but maximum coronary flow velocity was significantly lower in the erectile dysfunction group (P=0.004) and in the impaired glucose metabolism group (P=0.019), as compared with controls. There was no difference between the erectile dysfunction and impaired glucose metabolism groups. Coronary flow velocity reserve was reduced in the erectile dysfunction group (P=0.026) compared to controls, but was similar compared to the impaired glucose metabolism group. In multivariate analysis including all groups, erectile dysfunction score was the only independent predictor of reduced coronary flow velocity reserve (P=0.020). The magnitude of early coronary endothelial and smooth muscle cell dysfunction in otherwise healthy men with erectile dysfunction was comparable to that of patients with impaired glucose metabolism: a well known risk factor for coronary artery disease.
Background: The use of two-dimensional echocardiography (2D echo) for detection of ischaemia is l... more Background: The use of two-dimensional echocardiography (2D echo) for detection of ischaemia is limited due to high user dependency. Longitudinal motion is sensitive for ischaemia and usable for quantitative measurement of longitudinal myocardial function but time consuming. Velocity tracking (VeT) is a new method that gives an easy three-dimensional understanding of both systolic and diastolic regional motion, using colour coded bullÕs eye presentation of longitudinal velocity, derived from colour coded tissue Doppler. The aim of this study was to test the accuracy of VeT in detecting ischaemia in non-ST-segment elevation myocardial infarction (NSTEMI) patients bedside. Methods: Twenty patients with NSTEMI and 10 controls were included. Echocardiography was performed within 24 h of symptoms and prior to coronary angiography. BullÕs eye plots presenting the peak systolic velocity (PSV) and the sum of PSV and the E-wave-velocity (PSV+E) were created using our developed software. VeT was compared to expert wall motion scoring (WMS) and bedside echo. We used the clinical conclusion based on ECG, angiography and clinical picture as Ôgold standardÕ. Results: Sensitivity for ischaemia with VeT (PSV+E) was 85% and specificity 60%. The corresponding sensitivities for expert WMS were 75% (specificity 40%). For regional analysis VeT and WMS showed comparable results with correct regional outcome in 11⁄20 of patients both superior to bedside echo. Conclusion: Velocity tracking is a promising technique that provides an easily understandable three-dimensional bullÕs eye plot for assessment of regional left ventricular longitudinal velocity with great potential for detection of regional dysfunction and myocardial ischaemia.
Background: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visu... more Background: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast Ò software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (b) and myocardial blood flow (Axb) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast Ò-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. Methods: Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue Ò infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast Ò-generated A, b and Axb images, at different time points during rest and stress, were blindly compared to SPECT. Results: We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, b and Axb image interpretation significantly identified ischaemia in all territories (area under the curve 0AE66-0AE80, P = 0AE001-0AE05). Combined A, b and Axb image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0AE63; P<0AE001. Conclusion: Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast Ò-generated images, especially by combined A, b and Axb image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.
Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scint... more Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scintigraphy for the detection of myocardial ischaemia in patients with stable coronary artery disease."
Studies seeking to validate real-time three-dimensional echocardiography (3DE) with regard to car... more Studies seeking to validate real-time three-dimensional echocardiography (3DE) with regard to cardiac function and dimensions have almost exclusively used apical views. However, it has never been examined whether apical views are preferable to parasternal or subcostal views. In the present study, we compared the feasibility of 3DE volumetric measurements of the four heart chambers in three different views. We included 40 patients planned for a routine two-dimensional transthoracic echocardiography examination (2DE). All patients were scanned with both 2DE and 3DE (Sonos 7500; Philips Medical Systems Andover, MA, USA). Parasternal, apical and subcostal views were used for 3DE. Volumes were calculated using manual tracing in 16 planes. 2DE was performed in parasternal longaxis, subcostal and apical four-and two-chamber views. Manual tracing was used for area calculations. To be judged fully traceable, 5⁄6 (85%) or more of the ventricular and atrial walls had to be adequately visualized in each plane. The left ventricle and left atrium were adequately visualized in the 3DE apical view in 34 (85%) and 40 (100%) patients, respectively. Visualization of the right atrium was adequate in 31 (78%) patients, whereas the right ventricle was adequately visualized in only 12 (30%) patients. The apical view of 3DE provided superior visualization of all four heart chambers compared with the parasternal and subcostal views, when applying a slight off-axis approach for both ventricles when needed. Thus, in the present study, there was no incremental value of assessment of chamber volumes in the parasternal and subcostal views.
Background Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stres... more Background Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia. Methods Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue® infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest. Results In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR...
Background: Cardiac time intervals have been described as a measure of cardiac performance, where... more Background: Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements. Methods: We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter-and intraventricular function of the heart by displaying the cardiac phases. Results: The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods. Conclusion: The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.
Background: Traditional echocardiographic methods like left ventricular ejection fraction(EF) and... more Background: Traditional echocardiographic methods like left ventricular ejection fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking (ST) based 2D strain carry important prognostic information in acute coronary syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its high time resolution, may further increase the prognostic value. Peak systolic velocity (PSV) of the basal segments of the left ventricle from TDI is a robust and user independent parameter. The aim was to investigate the prognostic value of PSV compared to EF, WMS, 2D strain and E/e'. Methods: Echocardiographic images were collected and post processed in 227 ACS patients. Additional clinical data was prospectively gathered and patients were followed for 3-5 years regarding the combined endpoint of death or re-admission due to ACS or heart failure. Results: The combined endpoint occurred in 85 (37%) patients. Those with an event had lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p<0.001). In a ROC analysis, the AUC was larger for PSV (0.75) than for EF (0.68), WMS (0.63), 2D strain (0.67) and E/e'(0.70). The combined endpoint increased with decreasing PSV. When adjusting for differences in baseline characteristics in a COX-regression model, PSV remained independently associated with outcome where the others did not. PSV was also less sensitive to image quality with fewer values missing or unacceptable for analysis. Conclusion: Peak systolic velocity (PSV) is a robust measurement that seems to have a strong and independent association with outcome compared to traditional echocardiographic measurements in ACS patients.
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Papers by Reidar Winter