Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: A quantitative approach to contrast stress echocardiography

Background: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. Methods: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). Results: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs; 4.0 +/- 2.5, P <=.001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P =.07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =.01). Conclusion: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging.

Screening for heart disease in diabetic subjects

Background The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction. Methods Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 10 1) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was. sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. Results Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients: Subclinical disease could not be predicted by BNP. Conclusions Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Electrodynamic heart model construction and ECG simulation

Objectives: In this paper, we present a unified electrodynamic heart model that permits simulations of the body surface potentials generated by the heart in motion. The inclusion of motion in the heart model significantly improves the accuracy of the simulated body surface potentials and therefore also the 12-lead ECG. Methods: The key step is to construct an electromechanical heart model. The cardiac excitation propagation is simulated by an electrical heart model, and the resulting cardiac active forces are used to calculate the ventricular wall motion based on a mechanical model. The source-field point relative position changes during heart systole and diastole. These can be obtained, and then used to calculate body surface ECG based on the electrical heart-torso model. Results: An electromechanical biventricular heart model is constructed and a standard 12-lead ECG is simulated. Compared with a simulated ECG based on the static electrical heart model, the simulated ECG based on the dynamic heart model is more accordant with a clinically recorded ECG, especially for the ST segment and T wave of a V1-V6 lead ECG. For slight-degree myocardial ischemia ECG simulation, the ST segment and T wave changes can be observed from the simulated ECG based on a dynamic heart model, while the ST segment and T wave of simulated ECG based on a static heart model is almost unchanged when compared with a normal ECG. Conclusions: This study confirms the importance of the mechanical factor in the ECG simulation. The dynamic heart model could provide more accurate ECG simulation, especially for myocardial ischemia or infarction simulation, since the main ECG changes occur at the ST segment and T wave, which correspond with cardiac systole and diastole phases.

Comparison of two-dimensional speckle and tissue velocity based strain and validation with harmonic phase magnetic resonance imaging

Two-dimensional (2-D) strain (epsilon(2-D)) on the basis of speckle tracking is a new technique for strain measurement. This study sought to validate epsilon(2-D) and tissue velocity imaging (TVI)based strain (epsilon(TVI)) with tagged harmonic-phase (HARP) magnetic resonance imaging (MRI). Thirty patients (mean age. 62 +/- 11 years) with known or suspected ischemic heart disease were evaluated. Wall motion (wall motion score index 1.55 +/- 0.46) was assessed by an expert observer. Three apical images were obtained for longitudinal strain (16 segments) and 3 short-axis images for radial and circumferential strain (18 segments). Radial epsilon(TVI) was obtained in the posterior wall. HARP MRI was used to measure principal strain, expressed as maximal length change in each direction. Values for epsilon(2-D), epsilon(TVI), and HARP MRI were comparable for all 3 strain directions and were reduced in dysfunctional segments. The mean difference and correlation between longitudinal epsilon(2-D) and HARP MRI (2.1 +/- 5.5%, r = 0.51, p < 0.001) were similar to those between longitudinal epsilon(TVI), and HARP MRI (1.1 +/- 6.7%, r = 0.40, p < 0.001). The mean difference and correlation were more favorable between radial epsilon(2-D) and HARP MRI (0.4 +/- 10.2%, r = 0.60, p < 0.001) than between radial epsilon(TVI), and HARP MRI (3.4 +/- 10.5%, r = 0.47, p < 0.001). For circumferential strain, the mean difference and correlation between epsilon(2-D) and HARP MRI were 0.7 +/- 5.4% and r = 0.51 (p < 0.001), respectively. In conclusion, the modest correlations of echocardiographic and HARP MRI strain reflect the technical challenges of the 2 techniques. Nonetheless, epsilon(2-D) provides a reliable tool to quantify regional function, with radial measurements being more accurate and feasible than with TVI. Unlike epsilon(TVI), epsilon(2-D) provides circumferential measurements. (c) 2006 Elsevier Inc. All rights reserved.

Influence of arterial compliance on presence and extent of ischaemia during stress echocardiography

Objective: To seek an association between total arterial compliance (TAC) and the extent of ischaemia at stress echocardiography. Design: Cohort study. Setting: Regional cardiac centre. Methods: 255 consecutive patients (147 men; mean (SD) age 58 (8)) presenting for stress echocardiography for clinical indications were studied. Wall motion score index (WMSI) was calculated and ischaemia was defined by an inducible or worsening wall motion abnormality. Peak WMSI was used to reflect the extent of dysfunction (ischaemia or scar), and Delta WMSI was indicative of extent of ischaemia. TAC was assessed at rest by simultaneous radial applanation tonometry and pulsed wave Doppler in all patients. Results: Ischaemia was identified by stress echocardiography in 65 patients (25%). TAC was similar in the groups with negative and positive echocardiograms (1.08 (0.41) v 1.17 (0.51) ml/ mm Hg, not significant). However, the extent of dysfunction was associated with TAC independently of age, blood pressure, risk factors, and use of a beta blocker. Moreover, the extent of ischaemia was determined by TAC, risk factors, and use of a b blocker. Conclusion: While traditional cardiovascular risk factors are strong predictors of ischaemia on stress echocardiography, TAC is an independent predictor of the extent of ischaemia.

Incremental cost-effectiveness of exercise echocardiography vs. SPECT imaging for the evaluation of stable chest pain

Aims Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. Methods and results We examined prognosis and cost-effectiveness of exercise echocardiography (n=4884) vs. SPECT (n=4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio = 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P < 0.0001) resulting in an incremental cost-effectiveness ratio of $32 381/LYS. Conclusion Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.

Accuracy of strain rate techniques for ientification of viability at dobutamine stress echo: A follow-up study after revascularization

Background. Myocardial viability (VM) assessment based on wall motion scoring (WMS) with dobutamine echo (DbE) is difficult and subjective. New quantitative techniques such as strain rate imaging (SRI) correspond with isotopic techniques but their ability to predict functional recovery (FR) after revascularization is unclear. Methods. Stable post-MI pts (n=43, age 63±9, EF 36±6%) underwent SRI during DbE. WMS evidence of VM was based on lowdose augmentation at DbE. SR, end-systolic strain (ESS), post-systolic strain (PSS) and timing were analyzed at rest and low dose in abnormal segts. Pts were followed for 9±12 months; FR was defined as segt improvement on post-revascularization images. Results: Of 180 segts with abnormal resting function, 83 showed FR and 97 did not. Resting parameters were not predictive of recovery; resting post-systolic shortening had a sensitivity and specificity

Can myocardial contrast echo provide incremental benefit to exercise echo? Implications of the intensity and duration of hyperaemia

Background. Stress myocardial contrast echo (MCE) is technically challenging with exercise (Ex) because of cardiacmovementandshort duration ofhyperemia.Vasodilators solve these limitations, but are less potent for inducing abnormal wall motion (WM). We sought whether a combined dipyridamole (DI; 0.56 mg/kg i.v. 4 min) and Ex stress protocol would enable MCE to provide incremental benefit toWManalysis for detection of CAD. Methods. Standard echo images were followed by real time MCE at rest and following stress in 85 pts, 70 undergoing quantitative coronary angiography and 15 low risk pts.WMAfrom standard and LVopacification images, and then myocardial perfusion were assessed sequentially in a blinded fashion. A subgroup of 13 pts also underwent Ex alone, to assess the contribution of DI to quantitative myocardial flow reserve (MFR). Results. Significant (>50%) stenoses were present in 43 pts, involving 69 territories. Addition of MCE improved SE sensitivity for detection of CAD (91% versus 74%, P = 0.02) and better appreciation of disease extent (87% versus 65%territories, P=0.003), with a non-significant reduction in specificity. In 55 territories subtended by a significant stenosis, but with no resting WM abnormality, ability to identify ischemia was also significantly increased by MCE (82% versus 60%, P = 0.002). MFR was less with Ex alone than with DIEx stress (2.4 ± 1.6 versus 4.0 ± 1.9, P = 0.05), suggesting prolongation of hyperaemia with DI may be essential to the results. Conclusions. Dipyridamole-exercise MCE adds significant incremental benefit to standard SE, with improved diagnostic sensitivity and more accurate estimation of extent of CAD.

Comparison between myocardial integrated backscatter and strain rate imaging in the quantitative assessment of subepicardial function post-myocardial infarction

Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.

36 monocyte subpopulations counts and associations with global longitudinal strain in st-elevation myocardial infarction patients with normal ejection fraction

Introduction - Monocytes, with 3 different subsets, are implicated in the initiation and progression of the atherosclerotic plaque contributing to plaque instability and rupture. Mon1 are the “classical” monocytes with inflammatory action, whilst Mon3 are considered reparative with fibroblast deposition ability. The function of the newly described Mon2 subset is yet to be fully described. In PCI era, fewer patients have globally reduced left ventricular ejection fraction post infarction, hence the importance of studying regional wall motion abnormalities and deformation at segmental levels using longitudinal strain. Little is known of the role for the 3 monocyte subpopulations in determining global strain in ST elevation myocardial infarction patients (STEMI). Conclusion In patients with normal or mildly impaired EF post infarction, higher counts of Mon1 and Mon2 are correlated with GLS within 7 days and at 6 months of remodelling post infarction. Adverse clinical outcomes in patients with reduced convalescent GLS were predicted with Mon1 and Mon2 suggestive of an inflammatory role for the newly identified Mon2 subpopulation. These results imply an important role for monocytes in myocardial healing when assessed by subclinical ventricular function indices. Methodology - STEMI patients (n = 101, mean age 64 ± 13 years; 69% male) treated with percutaneous revascularisation were recruited within 24 h post-infarction. Peripheral blood monocyte subpopulations were enumerated and characterised using flow cytometry after staining for CD14, CD16 and CCR2. Phenotypically, monocyte subpopulations are defined as: CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3). Phagocytic activity of monocytes was measured using flow cytometry and Ecoli commercial kit. Transthoracic 2D echocardiography was performed within 7 days and at 6 months post infarct to assess global longitudinal strain (GLS) via speckle tracking. MACE was defined as recurrent acute coronary syndrome and death. Results - STEMI patients with EF ≥50% by Simpson’s biplane (n = 52) had GLS assessed. Using multivariate regression analysis higher counts of Mon1 and Mon 2 and phagocytic activity of Mon2 were significantly associated with GLS (after adjusting for age, time to hospital presentation, and peak troponin levels) (Table 1). At 6 months, the convalescent GLS remained associated with higher counts of Mon1, Mon 2. At one year follow up, using multivariate Cox regression analysis, Mon1 and Mon2 counts were an independent predictor of MACE in patients with a reduced GLS (n = 21)

Engineering thin films of magnetic alloys and semiconductor oxides at the nanoscale

The thesis aims to exploit properties of thin films for applications such as spintronics, UV detection and gas sensing. Nanoscale thin films devices have myriad advantages and compatibility with Si-based integrated circuits processes. Two distinct classes of material systems are investigated, namely ferromagnetic thin films and semiconductor oxides. To aid the designing of devices, the surface properties of the thin films were investigated by using electron and photon characterization techniques including Auger electron spectroscopy (AES), X-ray photoelectron spectroscopy (XPS), grazing incidence X-ray diffraction (GIXRD), and energy-dispersive X-ray spectroscopy (EDS). These are complemented by nanometer resolved local proximal probes such as atomic force microscopy (AFM), magnetic force microscopy (MFM), electric force microscopy (EFM), and scanning tunneling microscopy to elucidate the interplay between stoichiometry, morphology, chemical states, crystallization, magnetism, optical transparency, and electronic properties. Specifically, I studied the effect of annealing on the surface stoichiometry of the CoFeB/Cu system by in-situ AES and discovered that magnetic nanoparticles with controllable areal density can be produced. This is a good alternative for producing nanoparticles using a maskless process. Additionally, I studied the behavior of magnetic domain walls of the low coercivity alloy CoFeB patterned nanowires. MFM measurement with the in-plane magnetic field showed that, compared to their permalloy counterparts, CoFeB nanowires require a much smaller magnetization switching field , making them promising for low-power-consumption domain wall motion based devices. With oxides, I studied CuO nanoparticles on SnO2 based UV photodetectors (PDs), and discovered that they promote the responsivity by facilitating charge transfer with the formed nanoheterojunctions. I also demonstrated UV PDs with spectrally tunable photoresponse with the bandgap engineered ZnMgO. The bandgap of the alloyed ZnMgO thin films was tailored by varying the Mg contents and AES was demonstrated as a surface scientific approach to assess the alloying of ZnMgO. With gas sensors, I discovered the rf-sputtered anatase-TiO2 thin films for a selective and sensitive NO2 detection at room temperature, under UV illumination. The implementation of UV enhances the responsivity, response and recovery rate of the TiO2 sensor towards NO2 significantly. Evident from the high resolution XPS and AFM studies, the surface contamination and morphology of the thin films degrade the gas sensing response. I also demonstrated that surface additive metal nanoparticles on thin films can improve the response and the selectivity of oxide based sensors. I employed nanometer-scale scanning probe microscopy to study a novel gas senor scheme consisting of gallium nitride (GaN) nanowires with functionalizing oxides layer. The results suggested that AFM together with EFM is capable of discriminating low-conductive materials at the nanoscale, providing a nondestructive method to quantitatively relate sensing response to the surface morphology.

Prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago Hospital.

Background: The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda. Methods: In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients\' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities. Results: Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46±15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9±5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06–1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001). Conclusion: Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes.

Clinical effect of intravenous thrombolysis combined with nicorandil therapy in patients with acute ST-segment elevation myocardial infarction

Purpose: To evaluate the effectiveness of intravenous thrombolysis in combination with nicorandil in the treatment of acute ST-segment elevation myocardial infarction (STEMI). Methods: Patients who developed acute STEMI and underwent intravenous thrombolysis in the hospital were selected and divided into observation group (n = 128) and control group (n = 114). Besides thrombolytic therapy, the observation group was also given 20 mg of nicorandil. The control group received conventional thrombolytic therapy only. Clinical effects and rehabilitation of patients were observed. Results: Cardiac troponin I (cTNI) level of the observation group was 4.0 ± 1.5, 8.3 ± 2.8 and 9.8 ± 3.9 after 4, 12 and 24 h, respectively, which is much lower than 5.8 ± 1.4, 11.4 ± 2.7 and 13.2 ± 4.2 in the control group (p < 0.05). ST-segment resolution of observation group was higher (44 ± 14, 52 ± 17, 69 ± 21 and 80 ± 18) % at different time points, compared with the control group (p < 0.05). The proportion of patients with Curtis-Walker score > 3 points, and ventricular wall motion score (4.70 %; 1.38 ± 0.11) in the observation group were both lower than those of the control group (21.00 %; 1.43 ± 0.15) (p < 0.05). The difference in adverse cardiac events between the observation group (N = 6, 4.70 %) and control group (N = 12, 10.50 %) was not statistically significant (p > 0.05) Conclusion: Combining intravenous thrombolysis with nicorandil therapy can enhance myocardial perfusion level, reduce myocardial damage, improve cardiac function and decrease risk of arrhythmia for acute STEMI patients.

Impact of bulk cardiac motion on right coronary MR angiography and vessel wall imaging.

The purpose of this study was to investigate the impact of in-plane coronary artery motion on coronary magnetic resonance angiography (MRA) and coronary MR vessel wall imaging. Free-breathing, navigator-gated, 3D-segmented k-space turbo field echo ((TFE)/echo-planar imaging (EPI)) coronary MRA and 2D fast spin-echo coronary vessel wall imaging of the right coronary artery (RCA) were performed in 15 healthy adult subjects. Images were acquired at two different diastolic time periods in each subject: 1) during a subject-specific diastasis period (in-plane velocity <4 cm/second) identified from analysis of in-plane coronary artery motion, and 2) using a diastolic trigger delay based on a previously implemented heart-rate-dependent empirical formula. RCA vessel wall imaging was only feasible with subject-specific middiastolic acquisition, while the coronary wall could not be identified with the heart-rate-dependent formula. For coronary MRA, RCA border definition was improved by 13% (P < 0.001) with the use of subject-specific trigger delay (vs. heart-rate-dependent delay). Subject-specific middiastolic image acquisition improves 3D TFE/EPI coronary MRA, and is critical for RCA vessel wall imaging.